| 1855 |
2SC (CRB239) |
S-(2-succinyl)-cysteine |
88342 |
Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) syndrome is an autosomal disorder caused by germline mutation in the fumarate hydratase (FH) gene on chromosome 1q43. HLRCC associated RCC is often aggressive with metastatic disease in 50% of patients at presentation, and identification of HLRCC is important in managing the disease. A subset of aggressive renal tumors have pathogenic alterations of fumarate hydratase (FH) that do not result in the loss of FH expression. Typically FH alterations are associated with aberrantly high levels of S-(2-succino)-cysteine (2SC) expression observed in the nucleus. FH and 2SC immunohistochemistry assays may be used in combination to identify these pathogenic conditions. This is useful in the diagnosis of renal cell carcinomas, cutaneous and uterine leiomyomas, that occur secondary to somatic or germline (hereditary leiomyomatosis and renal cell cancer: HLRCC syndrome) alterations of the FH gene. |
| 1856 |
ACTH (P) |
Adrenocorticotropic hormone |
88342 |
CTH or Adrenocorticotropic hormone is synthesized from pre-pro-opiomelanocortin (pre-POMC). ACTH is produced and secreted from corticotrophs in the anterior lobe (or adenohypophysis) of the pituitary gland. The anti-ACTH immunohistochemical reagent could be useful in the study of neoplastic and non-neoplastic pituitary diseases. |
| 1857 |
Actin (Alpha SM) (1A-4) |
SMA, Smooth Muscle Actin |
88342 |
Smooth muscle actin, mouse monoclonal 1A4, labels smooth muscle cells, myofibroblasts, and myoepithelial cells, and is a useful tool for the identification of leiomyomas, leiomyosarcomas, and pleomorphic adenomas. Cytoplasmic actins, which belong to the microfilament system of cytoskeleton proteins, are some of the most conserved eukaryotic proteins being expressed in mammals and birds. The actin protein consists of six isoforms, varying in their amino acid sequence, but all having the same molecular mass of 42 kDa. The isoforms show more than 90% overall sequence homology, but only 50-60% homology in their 18 N-terminal residues. The N-terminal region appears to be a major antigenic region. There are different α isoforms specific for muscle tissues, i.e. skeletal muscle α, cardiac muscle α, and smooth muscle α, respectively. The β- and γ-actins may be present in muscle cells as well as most other cell types in the body, including non-muscle cells. |
| 1858 |
Actin (HHF35) |
Muscle Specific Actin |
88342 |
Muscle specific actin (MSA), a highly conserved, ubiquitous cytoskeletal protein of muscle and nonmuscle cells, exists in three isotypes (α, β, γ) that differ by their amino acid sequences and isoelectric points. Actin does not react with the α-actin of non-muscle (endothelial cells) sources. Gel electrophoresis and immunoblots show the specificity of HHF35 to be for the α- and γ-actin isotypes of skeletal, cardiac and smooth muscle. Can be used to differentiate leiomyosarcoma (MSA+, keratin -) from spindle cell carcinoma (MSA-, keratin +). |
| 1859 |
Adenovirus (20/11 & 2/6) |
none known |
88342 |
Adenoviruses are medium-sized (90-100 nm), non-enveloped icosohedral viruses with double-stranded DNA. More than 50 types of immunologically distinct adenoviruses can cause infections in humans. Adenoviruses are relatively resistant to common disinfectants and can be detected on surfaces, such as doorknobs, objects, and water of swimming pools and small lakes. Adenoviruses most commonly cause respiratory illness. The illnesses can range from the common cold to pneumonia, croup, and bronchitis. Depending on the type, adenoviruses can cause other illnesses such as gastroenteritis, conjunctivitis, cystitis, and, less commonly, neurological disease. People with weakened immune systems, such as following transplant surgery, are at high risk for developing severe illness caused by adenovirus infection. Some people infected with adenoviruses, especially those who have weakened immune systems, can have ongoing infections in their tonsils, adenoids, and intestines that do not cause symptoms. They can shed the virus for weeks or longer. |
| 1860 |
ADH5 |
CK5/14 + p63 + CK7/18 |
88344 |
The ADH5 (CK5/14 + p63 + CK7/18) cocktail is comprised of mouse monoclonal anti-CK5, anti-CK14, and anti-p63 antibodies and rabbit monoclonal anti-CK7 and anti-CK18 antibodies. CK5 and CK14 are high molecular weight keratins expressed in the cytoplasm of basal cells and myoepithelium of breast tissue. p63 is a transcription factor present in the nuclei of myoepithelial cells. CK7 and CK18 are low molecular weight cytokeratins primarily expressed in luminal cells of the breast. The IHC stains for CK5, CK14, p63, CK7 and CK18 have routinely been used as markers to complement morphological evaluation in the assessment of breast lesions, due to the differential expression of the luminal versus basal and myoepithelial markers. Cases of usual ductal hyperplasia (UDH) have been associated with expression of the basal cell markers, intermixed with cells expressing the keratins of luminal cells (mosaic pattern). Most cases of atypical ductal hyperplasia (ADH) and ductal carcinoma in situ (DCIS) are positive for myoepithelial cells (p63 and CK5/14) and exhibited an immunophenotype indicative of weak luminal cells. Additionally, the basal phenotype has been shown to be characterized by luminal expression of the basal and myoepithelial markers, using a cocktail of CK5, CK14 and p63. IHC, using CK5, CK14, p63, CK7 and CK18 antibodies, evaluated in combination with hematoxylin and eosin (H&E), has been shown to significantly increase inter-observer agreement amongst pathologists, compared to H&E alone |
| 1861 |
Adipophilin (BSB-91) |
PLIN2, Perilipin 2, ADRP |
88342 |
Adipophilin (also known as PLIN2) detects expression of adipocyte differentiation-related protein (ADRP/ADFP) in sebocytes and sebaceous lesions. Adipophilin is a useful marker in the identification of intracytoplasmic lipids, seen commonly in sebaceous lesions. Sebaceous carcinomas is an uncommon cutaneous malignancy that can be difficult to diagnose, especially when poorly differentiated. Utilization of adipophilin to highlight sebocytes can be useful in making this rare and challenging diagnosis |
| 1862 |
AE1 & 3 (AE1/3) |
Pankeratin, Cytokeratin AE1/AE3 |
88342 |
Keratins are a group of water-insoluble proteins that form monofilaments, a class of intermediate filament. These filaments form part of the cytoskeletal complex in epidermis and in most other epithelial tissues. Nineteen human epithelial keratins are resolved with two-dimensional gels electrophoresis. These can be divided into acid (pI <5.7) and basic (pI >6.0) subfamilies. The acidic keratins have molecular weights of 56.5, 55, 51, 50, 50`, 48, 46, 45, and 40 kD. The basic keratins have molecular weights of 65-67, 64, 59, 58, 56, and 52 kD. Members of the acidic and basic subfamilies are found together in pairs. The composition of keratin pairs varies with the epithelial cell type, stage of differentiation, cellular growth environment, and disease state: • The 56.5/65-67 kD pair is present in keratinized (differentiated) epidermis. • The 55/64 kD pair is characteristic of normal (corneal-type) epithelial differentiation. • The 51/59 kD pair is characteristic of the stratified squamous epithelial of internal organism such as esophagus and tongue. |
| 1863 |
AFP (P) |
Alpha-fetoprotein |
88342 |
Positive results may aid in the identification of non-neoplastic and neoplastic liver disease, yolk sac tumors and mixed germ cell tumors. AFP is a 70 kDa glycoprotein containing 590 amino acid residues. Cells of the embryonic yolk sac, fetal liver, and fetal intestinal tract synthesize this glycoprotein. AFP is a very useful marker for the detection of numerous developmental defects and various pathologies, whether cancerous or not. Expression of AFP has been demonstrated in about 44% of hepatocellular carcinomas, and in gonadal and extragonadal germ cells tumors, including yolk sac tumors. AFP has not been detected in normal adult tissue by immunostaining. However, traces of AFP are found in normal adult sera and in greater concentrations in maternal and fetal sera and amniotic fluid. |
| 1864 |
ALK (D5F3) |
Anaplastic lymphoma kinase, ALK Protein, CD246 |
88342 |
Anaplastic lymphoma kinase (ALK) is a tyrosine kinase receptor for pleiotrophin (PTN), a growth factor involved in embryonic brain development. In ALK-expressing cells, PTN induces phosphorylation of both ALK and the downstream effectors IRS-1, Shc, PLCγ, and PI3 kinase. ALK was originally discovered as a nucleophosmin (NPM)-ALK fusion protein produced by a translocation. Investigators have found that the NPM-ALK fusion protein is a constitutively active, oncogenic tyrosine kinase associated with anaplastic lymphoma. Research literature suggests that activation of PLCγ by NPM-ALK may be a crucial step for its mitogenic activity and involved in the pathogenesis of anaplastic lymphomas. A distinct ALK oncogenic fusion protein involving ALK and echinoderm microtubule-associated protein like 4 (EML4) has been described in the research literature from a non-small cell lung cancer (NSCLC) cell line, with corresponding fusion transcripts present in some cases of lung adenocarcinoma. The short, amino-terminal region of the microtubule-associated protein EML4 is fused to the kinase domain of ALK. Investigators have identified ALK translocations with other fusion partners, such as TRK- fused gene (TFG) and KIF5B, which have also been associated with NSCLC. In particular, the EML4-ALK fusion protein has been found in 3-7% of NSCLC samples. |
| 1865 |
ALK-1 (ALK-1) |
Anaplastic lymphoma kinase, ALK Protein, CD246 |
88342 |
The antibody labels normal human ALK protein and the NPM-ALK chimeric protein, and is a useful tool for the identification of the subgroup of anaplastic large-cell lymphomas (ALCL) that are ALK positive. The wild-type anaplastic lymphoma kinase (ALK) protein is a 200 kDa transmembrane receptor tyrosine kinase (4). Postnatal ALK expression is restricted to a few scattered cells in the nervous system (some glial cells and neurons, and a few endothelial cells and pericytes). About 72.5% of ALK-positive ALCL are associated with a (2;5) chromosomal translocation, where the nucleophosmin (NPM) gene located at 5q35 fuses with the ALK gene located at 2p23. With the fusion, the portion of the NPM gene encoding the N-terminal part of the NPM protein is juxtaposed to the part of the ALK gene that codes for the entire cytoplasmic region of the ALK protein. As a consequence, the ALK gene comes under the control of the NPM promoter, which induces a permanent and ubiquitous transcription of the NPM-ALK hybrid gene, resulting in the production of a 80 kDa NPM-ALK chimeric protein. In 3 large series of ALCL, 15-28% of chimeric ALK-positive lymphomas were negative for the t(2;5) translocation, and the main alternative fusion gene was identified as the tropomyosin 3 gene representing 17.5% of the ALK-positive ALCL cases. |
| 1866 |
AMACR (SP116) |
Racemase, p504S |
88342 |
AMACR (p504s) is normally negative or only very faintly expressed in normal glands of the prostate. In contrast, 80% or more of invasive adenocarcinomas show luminal cytoplasmic expression of p504S (AMACR). Immunohistochemistry for AMACR therefore assists in the diagnosis of prostate adenocarcinoma. |
| 1867 |
AMYLOID KAPPA (P) |
Kappa Free Light Chains |
88342 |
Immunoglobulins are composed of four protein chains: two light chains (either kappa or lambda light chains), and two heavy chains, of which there are several types. These proteins are produced by the plasma cells in the bone marrow. In AL patients, these plasma cells produce an abnormal antibody (immunoglobulin) protein. For AL amyloidosis, it is the “light chains” that become misfolded, and the abnormal, misfolded result is the forming of amyloid. With AL amyloidosis, the “A” is for amyloid and the “L” is for light chain. These misfolded amyloid proteins are deposited in and around tissues, nerves and organs. As the amyloid builds up in an organ, nerve or tissue, it gradually causes damage and affects their function. Each amyloidosis patient has a different pattern of amyloid deposition in their body. It often affects more than one organ. AL amyloidosis does not affect the brain. |
| 1868 |
AMYLOID LAMBDA (P) |
Lambda Free Light Chains |
88342 |
Immunoglobulins are composed of four protein chains: two light chains (either kappa or lambda light chains), and two heavy chains, of which there are several types. These proteins are produced by the plasma cells in the bone marrow. In AL patients, these plasma cells produce an abnormal antibody (immunoglobulin) protein. For AL amyloidosis, it is the “light chains” that become misfolded, and the abnormal, misfolded result is the forming of amyloid. With AL amyloidosis, the “A” is for amyloid and the “L” is for light chain. These misfolded amyloid proteins are deposited in and around tissues, nerves and organs. As the amyloid builds up in an organ, nerve or tissue, it gradually causes damage and affects their function. Each amyloidosis patient has a different pattern of amyloid deposition in their body. It often affects more than one organ. AL amyloidosis does not affect the brain. |
| 1869 |
Androgen Receptor (AR441) |
AR, NR3C4 (nuclear receptor subfamily 3, group C, member 4) |
88342 |
Androgen receptor is an intracellular protein that mediates the biological actions of physiological androgens such as testosterone and 5 α-dihydrotestosterone, which are essential for differentiation, development, and maintenance of the male reproductive organs. Complexes of androgen and its receptor regulate growth responses in accessory sex organs by modulating specific gene transcription. In anatomic pathology detection of androgen receptor by immunohistochemistry has been used as a marker for neoplasms of prostate origin. The cells in these tissues show a nuclear pattern of expression of the androgen receptor. |
| 1870 |
Annexin A1 (MRQ-3) |
ANXA1 |
88342 |
Annexin A1 is a monomeric, amphipathic protein containing 346 amino acids, originally purified from the peritoneal lavage of rats treated with glucocorticoids. This protein is expressed in multiple types of cells. In neutrophils and mast cells Annexin A1 is detected in granules, in macrophages in the cytoplasm, but depending on the activation state of the cells Annexin A1 can also be seen in the membranes and nuclei. Generally, Annexin A1 is thought to be a suppressor of the innate immune system by acting on neutrophils, mast cells and macrophages and inhibiting the cell traffic and the release of the granules. In lymphoproliferative disorders Annexin A1 has been shown to be highly specific for hairy cell leukemia, as no other B-lineage neoplasms express Annexin A1. Myeloid and mast cells in the specimens are usually reliable internal positive controls. |
| 1871 |
ARID1A (EP303) |
AT-Rich Interaction Domain 1A, BAF250 |
88342 |
The AT-Rich Interaction Domain 1A (ARID1A) is a crucial component of the SWI/SNF chromatin remodeling complex, playing a pivotal role in the regulation of gene expression. Aberrations in ARID1A expression have been documented in various malignancies, particularly in gynecologic tumors such as ovarian clear cell carcinoma, uterine endometrioid carcinomas, and carcinosarcomas. Additionally, ARID1A abnormalities have been reported in pancreatic ductal adenocarcinomas and primary liver malignancies. Immunohistochemistry for ARID1A emerges as a valuable diagnostic tool, showcasing loss of nuclear expression in a subset of malignancies. This serves as a pertinent prognostic and therapeutic marker, aiding in clinical decision-making and facilitating enrollment in clinical trials. |
| 1872 |
Arginase-1 (SP156) |
ARG-1 |
88342 |
Hepatocellular carcinoma (HCC) is the most common primary malignant tumor of the liver accounting for an estimated 70-85% of total liver cancers worldwide. The incidence is increasing in the West due to the burden of chronic hepatitis C infection &steatohepatitis attributed to obesity. Arginase-1 is a key urea cycle metalloenzyme that has demonstrated expression in normal human liver with a high degree of specificity. In sections of normal liver, anti-arginase-1 produced strong, diffuse cytoplasmic reactivity in all hepatocytes throughout the lobule. In a small percentage of cases, patchy nuclear reactivity is also evident in hepatocytes along with the strong cytoplasmic reactivity. There is no reactivity in bile duct epithelial cells, sinusoidal endothelial cells, Kupffer cells or vascular endothelial cells. In sections of HCC, anti-arginase-1 produces either cytoplasmic or cytoplasmic plus nuclear reactivity. |
| 1873 |
ATRX (P) |
Alpha-thalassemia/mental retardation X-linked gene, XH2, XNP |
88342 |
Alpha-thalassemia/mental retardation X-linked (ATRX) gene is mutated in high grade astrocytomas, as opposed to oligodendrogliomas, oligoastrocytomas and glioblastomas. This phenotype characterized by loss of function of ATRX has been called alternative lengthening of telomeres and has been identified in approximately 25% of total high grade astrocytomas (20-40%, depending on the study). In combination with other makers such as IDH1, 1p, 19q, ATRX is incorporated in a diagnostic algorithm that appears to better characterize the outcome of cases of astrocytomas. |
| 1874 |
B72.3 (TAG-72) (B72.3) |
TAG-72, Tumor associated glycoprotein 72 |
88342 |
Tumor associated glycoprotein (TAG)-72 is a high molecular weight glycoprotein that is present on the surface of many neoplastic cells, including adenocarcinomas of the breast, colon, and lung. TAG-72 is found in lung adenocarcinoma and is absent in mesothelioma, making the TAG-72 antibody useful in distinguishing adenocarcinoma from mesothelioma.1,2 The B72.3 mouse monoclonal antibody was previously validated in the Immunohistochemistry laboratory using antibody purchased from Biogenex (San Ramon, CA). Because antibody was no longer available from Biogenex, this study is performed to evaluate the performance of the B72.3 monoclonal antibody purchased from Ventana (supplied by Cell Marque, Rocklin, CA) |
| 1875 |
BAP1 (C4) |
BRCA1-Associated Protein 1, ubiquitin carboxyl-terminal hydrolase BAP1, ubiquitin carboxyl-terminal hydrolase like-2 (UCHL2) |
88342 |
BRCA-1 gene and BRCA1-associated protein 1 (BAP1) are expressed in most tissues.5 BAP1 functions as a deubiquitinase. By removing ubiquitin, BAP1 helps regulate the function of many proteins involved in diverse cellular processes. The BAP1 protein is thought to help control cell proliferation and death. Studies suggest that it is involved in the progression of cells through the cell cycle and that it plays roles in repairing damaged DNA and controlling the activity of genes.4 Mutations within the BRCA1 gene, and the associated loss of BAP1 expression, are believed to account for approximately 45% of families with increased incidence of both early-onset breast cancer and ovarian cancer. The BRCA1 gene is expressed in numerous tissues, including breast and ovary, and encodes a predicted protein of 1,863 amino acids. BAP1 has been shown to bind to the N-terminus of BRCA1 and is a potential mediator of tumor suppression. BAP1 is a ubiquitin hydrolase and has been shown to enhance BRCA1-mediated cell growth suppression. The absence of BAP1 in epithelioid melanocytes suggests the possibility of a germline mutation. Patients with these BAP1 germline mutations are more susceptible to a range of neoplasms including mesothelioma (without occupational or environmental asbestos exposure), uveal and cutaneous melanoma, atypical Spitz tumor (AST), clear cell renal carcinoma, and basal cell carcinoma. These loss-of-function mutations translate to loss of BAP1 expression in tumor cells by immunohistochemistry. BAP1 loss is also useful in distinguishing malignant mesothelioma from benign mimics. BAP1 is expressed in all benign mesothelial proliferations, whereas 66% of mesotheliomas demonstrate BAP1 loss. In analyzing the contribution of BAP1 in the development of sporadically acquired melanocytic lesions, a subset of ASTs, uveal melanomas, and cutaneous melanomas showed somatically acquired BAP1 mutations and the associated loss of BAP1 protein expression. |
| 1876 |
BCL-2 (124) |
B cell lymphoma 2 |
88342 |
The assessment of bcl-2 expression by immunohistochemical (IHC) staining is useful in the assessment of hematologic neoplasms including follicular lymphoma, diffuse large B-cell lymphoma, and Burkitt lymphomas. Anti-BCL2 has shown consistent negative reaction on reactive germinal centers and positive staining of neoplastic follicles in follicular lymphoma. Consequently, this antibody is valuable when distinguishing between reactive and neoplastic follicular proliferation in lymph node biopsies. |
| 1877 |
BCL2 EP36 (EP36) |
B cell lymphoma 2 |
88342 |
The Bcl-2 family of proteins regulates apoptosis by controlling mitochondrial permeability and release of cytochrome c. Bcl-2 is an anti-apoptotic protein that resides in the outer mitochondrial wall and inhibits release of cytochrome c. Over-expression of Bcl-2 has been shown to promote cell survival by suppressing apoptosis. It has been documented that bcl-2 becomes deregulated in tumor cells as a result of translocation into the immunoglobulin heavy-chain locus and is therefore activated in B cell malignancies. Bcl-2 antibody is useful in differentiation of follicular lymphoma from reactive follicular proliferation (bcl-2 negative). In addition, bcl-2 expression has been shown to be correlated with disease prognosis in breast cancer, prostate cancer, ovarian cancer, endometrial cancer and colon cancer. |
| 1878 |
BCL-6 (LN22) |
B cell lymphoma 6 protein |
88342 |
BCL6 is a transcriptional regulator gene which codes for a 706-amino-acid nuclear zinc finger protein. In normal tissue these antibodies have strong nuclear staining for a subset of B-lymphocytes, mostly located in germinal centers (GC). BCL6 antibodies stain malignant cells in follicular lymphoma, diffuse large B-cell lymphomas, Burkitt lymphoma, classical Hodgkin lymphoma, as well as a majority of tumor cells in nodular lymphocyte predominant Hodgkin lymphoma. BCL6 expression has been also seen in anaplastic large cell lymphomas (ALCL). |
| 1879 |
beta-Amyloid (RBT-A4) |
Amyloid beta-protein, Amyloid β-peptide, Aβ, βA4 protein |
88342 |
Detection of neurofibrillary tangles and amyloid pathology are required for the diagnosis of Alzheimer’s disease. Both tangles and plaques may be detected by histochemical stains or by immunohistochemistry. Guidelines published by the National Institute of Aging and Alzheimer’s Association recommend that IHC analysis be used for the detection of plaques and tangles rather than histochemical analyses, such as Thioflavin S or Bielschowsky stains. |
| 1880 |
beta-Catenin (14) |
Catenin-beta-1 |
88342 |
Β-catenin is part of the Wnt signaling pathway - a highly conserved pathway with a critical role in embryonic development, carcinogenesis, and epithelial-to-mesenchymal transition. On Wnt activation, β-catenin is translocated from the membrane to the cytoplasm and nucleus. In the colon, β-catenin plays a critical role in tumorigenesis; in the thyroid, the pathway is important for anaplastic and possibly papillary thyroid carcinomas; in the uterus, endometrioid endometrial carcinoma is associated with β-catenin mutations. It is used to classify hepatocellular adenoma subtypes and distinguish them from focal nodular hyperplasia. It is used to identify isolated tumor cells in neuroblastoma. Reactive fibroblast proliferations are negative while desmoid fibromatosis has a nuclear staining. In colon cancer, proliferations of fibroblasts with positive nuclei indicate Gardner syndrome. |
| 1881 |
BOB-1 (P) |
OBF-1, Oct binding factor-1 |
88342 |
BOB.1, also known as Oct-binding factor-1, is a B-cell transcription factor. In normal tissues, germinal center B-cells strongly express nuclear BOB.1 with weaker staining seen in non-germinal center B-cells. Immunohistochemical staining for BOB.1, in conjunction with another B-cell transcription factor, OCT-2, is useful in the differential diagnosis of classical Hodgkin lymphoma. OCT-2 and BOB1 are both expressed in nodular lymphocyte-predominant Hodgkin lymphoma and with varying intensity in most B-cell non-Hodgkin lymphomas. In contrast, expression of BOB.1, OCT-2, or both, is lost in the malignant cells of classical Hodgkin lymphoma. |
| 1882 |
BRACHYURY (1H9A2) |
Bry, TBXT, T-Box Transcription Factor T |
88342 |
Brachyury is involved in the transcriptional regulation of genes required for mesoderm formation and differentiation. When bound to the T site, activates gene transcription. Genetic variations are associated with susceptibility to neural tube defects and the development of chordoma. Chordoma is a rare, clinically malignant tumors derived from notochordal remnants. They are characterized by slow growth, local destruction of bone, extension into adjacent soft tissues and rarely distant metastatic spread. |
| 1883 |
BRAF (VE-1) |
BRAF mutated V600E |
88342 |
BRAF is the product of a proto-oncogene located on chromosome 7q34. It is a serine/threonine kinase that plays a role in the MAP/ERK signaling cascade. Mutations involving BRAF have been described in numerous neoplasms, BRAF V600E mutation being the most common. This mutation has been described in hairy cell leukemia, Langerhans cell histiocytosis, melanoma, and thyroid and colon carcinomas. |
| 1884 |
C3d (P) |
Complement 3d |
88342 |
Complement component C3 plays a central role in the activation of complement system. Its activation is required for both classical and alternative complement activation pathways. C3d deposition in the renal transplant PTCs (peritubular capillaries) is indicative of AMR (antibody-mediated rejection) with subsequent high probability of graft loss. Anti-C3d, combined with anti-C4d, can be utilized as a tool for diagnosis of AMR and warrant prompt and aggressive anti-rejection treatment. In another study, anti-C3d labeled the epidermal basement membrane in 97% (31/32) cases of bullous pemphigoid (BP), with none of the normal controls demonstrating such findings. In the same study 27% (3/11) cases of pemphigus vulgaris (PV) demonstrated intercellular C3d deposition. Therefore, C3d immunohistochemistry is a helpful adjunct in the diagnosis of BP (and perhaps PV), especially in the cases in which only formalin-fixed, paraffin embedded tissue is available for analysis. |
| 1885 |
C4d (P) |
Complement 4d |
88342 |
Complement split product C4d is generated during activation of classic complement pathway. C4d is a stable product that stays bound to the target for weeks facilitating detection on sampled tissues. The protein is expressed as a single chain precursor which is proteolytically cleaved into a trimer of alpha, beta, and gamma chains prior to secretion. C4d is a widely used tool in establishing the diagnosis of antibody-mediated rejection in solid organ transplantation (kidney, liver, heart, small intestine, and lung). Capillary deposition of C4d is a marker of antigen-antibody interaction and complement activation, and hence antibody-mediated rejection. |
| 1886 |
Calcitonin (P) |
CT, thyrocalcitonin |
88342 |
The antibody labels calcitonin-producing C-cells. Antibodies to calcitonin have been shown to aid in the classification of MTC. Calcitonin (CT) is a 32 amino acid peptide hormone derived from a precursor consisting of 136 amino acids and an N-terminal leader sequence. CT contains a carboxyterminal proline amide and a disulphide bridge between cysteine residues at position 1 and 7. The sequence is highly conserved in a variety of species within the N-terminal loop region but demonstrates divergence in the rest of the sequence. CT is produced in the parafollicular C-cells of the thyroid and acts through its receptors (CTR) inhibiting osteoclast-mediated bone resorption and increasing calcium excretion by the kidney. Accumulating evidence supports the existence of non-thyroidal CT-like peptides in tissues such as brain, prostate and uterus, which suggest additional physiological roles of CT. Medullary thyroid carcinoma (MTC) may be sporadic or familial, the latter has an autosomal dominant pattern of inheritance. |
| 1887 |
Calponin (CALP) |
Calponin-1, Basic calponin |
88342 |
Calponin is a calmodulin, F-actin and tropomyosin binding protein which is thought to be involved in the regulation of smooth muscle contraction. Calponin expression is restricted to smooth muscle cells and has been shown to be a marker of the differentiated (contractile) phenotype of developing smooth muscle. |
| 1888 |
CALRETICULIN (CAL2) |
CALR |
88342 |
CALR mutations are detectable in 67% of essential thrombocythemia (ET) and 88% of primary myelofibrosis (PMF) cases negative for mutations involving JAK2 or MPL genes. Myelodysplastic syndromes overlap neoplasms, chronic myelogenous leukemia or reactive processes are not associated with CALR mutations. When mutated, calreticulin can be detected by immunohistochemistry in the cytoplasm of megakaryocytes in the bone marrow. In consequence, the immunohistochemical stain for calreticulin is useful in the diagnosis of myeloproliferative neoplasms JAK2 or BCR-ABL1 negative. NOTE: Cytoplasmic staining of megakaryocytes indicates the presence of CALR mutation. The absence of CALR mutation is indicated when all megakaryocytes remain unlabeled. |
| 1889 |
Calretinin (P) |
Calbindin |
88342 |
Calretinin, a calcium-binding protein with a molecular weight of 29 kD, is a member of the large family of EF-hand proteins that also include S-100 protein. EF-hand proteins are characterized by a helix-loop-helix fold that acts as the calcium-binding site. Calretinin contains six such EF-hand stretches. It is abundantly expressed in central and peripheral neural tissues especially in the retina and neurons of the sensory pathways. Calretinin is also consistently expressed in normal and reactive mesothelial cell lining of all serosal membranes, eccrine glands of skin, convoluted tubules of kidney, Leydig and Sertoli cells of the testis, endometrium and ovarian stromal cells and adrenal cortical cells. Calretinin is also a sensitive and specific indicator of normal and reactive mesothelial cells in effusion cytology. In addition, calretinin is expressed in nerve fibers in the lamina propria of patients without Hirschsprung disease, but expression is lost in patients with Hirschsprung disease. |
| 1890 |
CAM 5.2 (CAM5.2) |
Cytokeratin CAM5.2 |
88342 |
Cytokeratin clone CAM5.2 has a primary reactivity with human keratin proteins that correspond to Moll’s peptides #7 and #8, Mr 48 and 52 kd respectively. Cytokeratin 7 and 8 are present on secretory epithelia of normal human tissue but not on stratified squamous epithelium. CAM5.2 stains most epithelial-derived tissue, including liver, renal tubular epithelium, and hepatocellular and renal cell carcinomas. CAM5.2 may not react with some squamous cell carcinomas. It is used to distinguish undifferentiated carcinoma from malignancies of nonepithelial origin such as lymphomas, melanomas, and sarcomas. |
| 1891 |
CAMTA 1 (P) |
Calmodulin Binding Transcription Activator 1 |
88342 |
Epithelioid hemangioendothelioma (EHE) is a malignant vascular neoplasm with significant potential for both local recurrence and metastasis. EHE is characterized by recurrent chromosomal translocations involving the regions 1p36.3 and 3q25. In about 90% of EHE cases, this translocation results in the formation of a WWTR1-CAMTA1 fusion gene. The fusion gene leads to overexpression of both the WWTR1 and CAMTA1 proteins. WWTR1 protein has been found to be expressed in diverse cell types, whereas CAMTA1 expression is normally limited to the brain. Therefore, CAMTA1 can be a useful diagnostic marker to distinguish EHE from a variety of other tumors with epithelioid morphology. Controversial results have been reported regarding the usefulness of CAMTA1 immunohistochemistry (IHC) in differential diagnosis of EHE and its histologic mimics. The reported specificity of CAMTA1 IHC is highly depending on the antibody used in the studies. |
| 1892 |
Carbonic Anhydrase IX (EP161) |
CA9, CAIX |
88342 |
Carbonic anhydrase (CA) is an enzyme that assists rapid interconversion of carbon dioxide and water into carbonic acid, protons, and bicarbonate ions. It is abundant in all mammalian tissues. Because of its functionality, it is a diagnostic marker for various cancers, most notably renal cell carcinoma (RCC). There are many genes that are inducible by hypoxia, and CAIX is one of the most inducible because of its stability and location within the membrane. CAIX a reliable histochemical marker of hypoxia. In normal human tissue CAIX expression is limited to gastric mucosa, biliary tract, small intestine and fetal tissues. It is overexpressed in a wide array of tumors, mostly around areas of necrosis or hypoxia. Squamous cell carcinomas (SCC) express abundant CAIX. In renal tumors, CAIX is detected in over 80% of clear cell RCC, with uneven distribution throughout the specimen, with intensities varying from dim to strong, over 50% of the positive cases being moderate. Papillary RCC is negative for CAIX. By immunohistochemistry CAIX has a cytoplasmic and membranous pattern of expression. |
| 1893 |
Cathepsin-K (3F9) |
CTSK |
88342 |
Cathepsin K is closely involved in osteoclastic bone resorption and may participate partially in the disorder of bone remodeling. Cathepsin K displays potent endoprotease activity against fibrinogen at acid pH and may play an important role in extracellular matrix degradation. Defects in Cathepsin K are the cause of pycnodysostosis (PKND) [MIM:265800]. PKND is an autosomal recessive osteochondrodysplasia characterized by osteosclerosis and short stature. Cathepsin K is a papain-like cysteine protease with high matrix-degrading activity. Studies suggest that its expression is under the control of mTOR pathway, a therapeutic target for a number of cancer types, and may serve as a marker for evaluating mTOR pathway activation. The perivascular epithelioid cell tumors (PEComas), also referred to as neoplasms of the perivascular epithelioid cells, are mesenchymal tumors composed of histologically and immunohistochemically distinctive perivascular epithelioid cells (PEC). The most common tumors in the PEComa family are renal angiomyolipoma (AML) and pulmonary lymphangioleiomyomatosis (LAM). Both AML and LAM are more common in patients with tuberous sclerosis complex (TSC), an autosomal dominant genetic disease caused by losses of TSC1 (9q34) or TSC2 (16p13.3) genes. The critical role of the TSC gene products is to regulate the Rheb/mTOR/p70S6K pathway and then govern cell growth and proliferation. Taken together, Cathepsin K could be upregulated in PEComas by TSC gene mutation via alteration of mTOR pathway and might be a marker assisting identification and confirmation of the diagnosis of this type of tumors. Strong expression of Cathepsin K has recently been reported in PEComa lesions in both kidney and lung. Therefore, we developed a protocol for performing Cathepsin K immunohistochemistry (IHC) staining and validated its use in aiding the differential diagnosis of renal AML versus clear cell renal cell carcinoma (CCRCC). |
| 1894 |
CD10 (56C6) |
CALLA (common acute lymphoblastic leukemia antigen) |
88342 |
CD10, common acute lymphoblastic leukemia antigen, is expressed by a subset of T follicular helper cells. It has a direct role in cell growth and apoptosis and has been implicated in tumor cell proliferation. CD10 expression has been reported in a variety of tissues including renal cell carcinoma, hepatocellular carcinoma, and follicular lymphoma. |
| 1895 |
CD103 (EPR4166(2)) |
Alpha E Integrin, Human mucosal lymphocyte antigen 1 |
88342 |
CD103 (alpha E integrin) is expressed by intraepithelial T lymphocytes in the intestine, tonsil and lung as well as some dendritic cells. CD103 is expressed by enteropathy-associated T-cell lymphomas which are thought to arise from intraepithelial lymphocytes. There is some variation in expression across T-cell lymphomas; however, this marker may still add diagnostic utility. CD103 is expressed in B-cell lymphoma by hairy cell leukemia and hairy-cell leukemia variant. In one study, it was 100% sensitive and specific for these entities when compared to other types of B-cell lymphoma. This evaluation can be performed by flow cytometry, but this assay may not have been performed in settings where the diagnosis was unsuspected or sufficient fresh material was not available for evaluation. |
| 1896 |
CD117 (c-kit) (P) |
KIT Proto-Oncogene, Receptor Tyrosine Kinase, c-kit |
88342 |
The antibody labels the transmembrane tyrosine kinase receptor CD117/c-kit, located in hematopoietic stem cells, melanocytes, mast cells, Cajal cells, germ cells, basal cells of skin, and mammary ductal epithelia. The antibody may be a useful tool for the identification of several cancers expressing c-kit, including mast cell diseases, acute myeloid leukemia (AML), small cell lung carcinoma (SCLC), and Ewing sarcoma, and it may aid in the differentiation between gastrointestinal stromal tumors (GISTs) and other intraabdominal mesenchymal tumors. |
| 1897 |
CD123 (7G3) |
IL-3Rα |
88342 |
Reacts with human CD123, the 70 kD IL-3 receptor α chain (IL-3Rα), which associates with the 120-140 kD β subunit. The β chain is shared with the receptors for interleukins IL-5 and GM-CSF. IL-3Rα is expressed on hematopoietic progenitors and plays an important role in hematopoietic progenitor cell growth and differentiation. This antibody has been reported to block the binding of 125I-IL-3 to high and low affinity IL-3 receptors. In functional experiments, this antibody was found to inhibit acute myeloid leukemia cell proliferation, basophil histamine release, endothelial cell-mediated IL-8 secretion, and neutrophil transmigration. At the Fifth HLDA Workshop, the human IL-3 receptor was designated CD123. CD123 is the IL3 receptor alpha chain. It is expressed on a variety of hematopoietic cells including myeloid lineage cells as well as plasmacytoid dendritic cells (DC2 cells). However, it is also expressed in some lymphoid malignancies such as hairy cell leukemia cells. In hairy cell leukemia, its expression appears to be quite specific. In fact, it is routinely assessed in the flow cytometric analysis of suspected hairy cell cases. Recently, CD123 has been reported to be expressed in blastic NK cell leukemia/lymphoma (CD56+ hematodermic neoplasm). This latter tumor is rare but arises in the differential diagnosis of blastic skin tumors and acute myeloid leukemia’s. |
| 1898 |
CD138 (B-B4) |
Syndecan-1 |
88342 |
CD138 (aka syndecan-1a) protein backbone is a single chain molecule of 30.5 kDa. Five putative GAG attachment sites exist in the extracellular domain. GAG fine structure appears to reflect the cellular source of the syndecan. Expression of CD138 in human hematopoietic cells is restricted to plasma cells in normal bone marrow. Early B-cell precursors in human bone marrow are CD138 negative. CD138 is also expressed in endothelial cells, fibroblasts, keratinocytes and normal hepatocytes. |
| 1899 |
CD14 (EP128) |
Leu M3 |
88342 |
Anti-CD14 labels a 55 kDa, glycosyl-phosphatidylinositol-linked membrane protein, involved in endotoxin binding and recognition of apoptotic cells. CD14 is expressed by monocytes and dermal dendritic cells; anti-CD14 is considered to be a macrophage-derived monocyte marker. CD14 is also present in granulocytes, endothelial, epithelial cells, and placental trophoblasts. In the spleen, CD14 can be expressed in the red pulp and marginal zone cells, and histiocytes around sheathed capillaries. In the lymph node, true sinusoidal histiocytes, and follicular dendritic cells stain with anti-CD14. However, other monocyte-derived cells in the lymph node, such as in sinusoidal histiocytosis with erythrophagocytosis, macrophages associated with anthracosis, germinal center tingible body macrophages in reactive germinal centers do not express CD14 antigen. CD14 is not expressed in plasmacytoid dendritic cells. Anti-CD14 positive histiocytes are reported as markedly increased in DLBCL, but not in chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL), mantle cell lymphoma (MCL), or follicular lymphoma (FL). Anti-CD14 is useful in identifying massive lymphadenopathy with sinus histiocytosis (Rosai-Dorfman disease) when used in a panel including anti-S100 and anti-CD68. Anti-CD14 can also be used for decalcified bone marrow biopsy specimens to show increased myelomonocytic and monocytic neoplastic cells in chronic myelomonocytic leukemia and monocytic leukemia, and is very helpful in the distinction of myeloproliferative neoplasms, myelodysplastic syndrome, and acute monocytic leukemia. This antibody is more sensitive for leukemic monocytic cells than antibodies directed against CD163 and CD68/PG-M1. |
| 1900 |
CD15 (BRA4F1) |
Blood group antigen Lewis X |
88342 |
CD15 (BRA4F1) reacts with human CD15 antigen present on myeloid cells, mainly granulocytes but not on B cells, T cells, monocytes, erythrocytes or platelets. It also reacts with Hodgkin's and Reed-Sternberg cells in individuals with Hodgkin's disease. |
| 1901 |
CD15 (MMA) |
Fucosyltransferase 4, FUT4 |
88342 |
CONFIRM anti-CD15 (MMA) recognizes lacto-N-fucopentose III. Antibodies against CD15 normally react in a strong cell surface membrane staining pattern with granulocytes and granulocyte precursors, monocytes, a subset of tissue macrophages, and activated T-lymphocytes. CONFIRM anti-CD15 (MMA) also reacts against the Reed-Sternberg cells of Hodgkin’s disease and, because it recognizes a carbohydrate antigen, is also expressed by a variety of carcinoma types but is negative in malignant mesotheliomas. In addition, CONFIRM anti-CD15 is a pertinent panel marker for thymoma, myxoinflammatory fibroblastic sarcoma, histiocytic lymphoma-sarcoma, peripheral T-cell lymphomas, anaplastic large cell lymphoma, and renal cell carcinoma. In an effort to promote standardization of diagnostic immunohistochemistry across laboratories, international multi-institutional groups have published a variety of best practices based on expert consensus recommendations. Guidelines published by the NordiQC proficiency testing consortium has provided recommendations for appropriate titration of CD15 immunohistochemistry. |
| 1902 |
CD163 (MRQ-26) |
M130 |
88342 |
CD163 is a hemoglobin scavenger receptor with variable expression in monocytes (low affinity) and tissue macrophages (high affinity). In its soluble form, it is an anti-inflammatory molecule and is important in inflammatory states such as rheumatoid arthritis and atherosclerosis. In tissues its specificity for the monocyte/macrophage lineage is superior to CD68. Diagnostically it may be useful as an additional monocyte/macrophage marker. For example, Nguyen and colleagues found that while CD68 was present in subsets of non-macrophage/monocyte tumors (i.e. vascular tumors, carcinoma, melanoma), CD163 was not expressed. It was present in many tumors of presumed monocyte/macrophage origin such as histiocytic sarcoma, Langerhans cell histiocytosis, Rosai-Dorfman disease, histiocytomas, and tenosynovial giant cell tumors. |
| 1903 |
CD19 (BT51E) |
B-Lymphocyte Surface Antigen B4 |
88342 |
CD19 is a transmembrane glycoprotein member of the immunoglobulin superfamily. It is considered to be one of the most reliable surface markers of B cell lineage over a wide range of maturational stages. Similar to the widely used B cell marker CD20, CD19 is also expressed on both normal and most B-cell lymphomas. However, in contrast to CD20 which has minimal expression on early pre-B cells and no expression on plasma cells, CD19 is also expressed in pre-B cells and normal plasma cells. CD19 immunohistochemical (IHC) staining can be an alternative or complementary test to the existing CD20 test, especially in the case when CD20 expression is reduced or absent. Anti-CD20 therapeutic antibodies such as Rituximab have direct impact on CD20. We developed a protocol for performing CD19 IHC staining and verified its usage in aiding diagnosis of B-cell lymphomas. |
| 1904 |
CD1a (O10) |
Leu6 |
88342 |
CD1a is an antigen-presenting protein that binds self and non-self lipid and glycolipid antigens and presents them to T-cell receptors on natural killer T-cells. CD1a is expressed on cortical thymocytes, epidermal Langerhans cells, dendritic cells, on certain T-cell leukemias, and in various other tissues. |
| 1905 |
CD2 (AB75) |
Lymphocyte function antigen 2 (LFA2) |
88342 |
The CD2 antigen, also known as lymphocyte function antigen2 (LFA2), is a single chain type I transmembrane molecule of about 50 kD and consists of 351 amino acids. It plays a critical role in activation of T cells. It binds to CD58 on antigen presenting cells and induces tyrosine phosphorylation of other molecules involved in T cell activation. It also plays a regulatory role in T-cell or NK-cell mediated cytolysis. CD2 antigen is expressed on majority of T cells in peripheral lymphoid tissue, NK cells, cortical thymocytes and most malignant cells of T cell origin. |
| 1906 |
CD20 (L26) |
MS4A1 |
88342 |
CD20 is a transmembrane, non-glycosylated protein expressed on B-cell precursors and mature B cells, but is lost following differentiation into plasma cells. In resting B cells, CD20 appears in a 33 kDa non-phosphorylated form. After mitogen stimulation, CD20 becomes heavily phosphorylated (35-37 kDa isoforms), and it is a dominant phosphoprotein in activated B cells, B-cell lines, and hairy cell leukemias. The long N- and C-terminal ends of the protein are located on the cytoplasmic side of the membrane and only a minor portion of the protein is exposed on the cell surface. Antibodies reacting with CD20 cytoplasmic epitopes are designated CD20cy. It is suggested that CD20 plays a direct role in regulating the transmembrane conductive Ca2+ flux of B cells which indicates a possible function for CD20 as a regulator of proliferation and differentiation. |
| 1907 |
CD200 (E5I9V) |
OX2 |
88342 |
CD200 is a member of the immunoglobulin superfamily expressed in a variety of cell types including B-cell and T-cell subsets, endothelial cells, and neurons. Within B-cell non-Hodgkin lymphomas, CD200 expression has been reported in >95% of cases of chronic lymphocytic leukemia and <5% of cases of mantle cell lymphoma, assisting in distinction of these two CD5 positive B-cell lymphoproliferative disorders. In addition, CD200 expression has been reported to be commonly expressed in primary mediastinal large B-cell lymphoma, assisting in the differential diagnosis with diffuse large B-cell lymphoma, not otherwise specified. |
| 1908 |
CD21 (1F8) |
CR2 |
88342 |
CD21, or complement receptor 2 (CR2) is the receptor for complement C3Dd, for the Epstein-Barr virus on human B-cells and T-cells, and for heterogeneous nuclear ribonucleoprotein U (HNRPU). It participates in B lymphocytes activation. Genetic variations in CR2 are associated with susceptibility to systemic lupus erythematosus type 9 (SLEB9) [MIM:610927]. Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with a complex genetic basis. SLE is an inflammatory, and often febrile multisystemic disorder of connective tissue characterized principally by involvement of the skin, joints, kidneys, and serosal membranes. It is thought to represent a failure of the regulatory mechanisms of the autoimmune system. |
| 1909 |
CD22(SP104) |
SIGLEC2, Sialic Acid-Binding Ig-Like Lectin 2, T-Cell Surface Antigen Leu-14 |
88342 |
CD22 is an approximately 135 kDa transmembrane glycoprotein, which plays a role in the regulation of B-cell function. Normal CD22 expression is observed in follicular mantle and marginal zone B-cells. Expression is low on germinal center B-cells and absent from plasmablasts and terminally differentiated plasma cells. CD22 is thought to play a role in localizing B-cells to lymphoid tissues. Almost all B-cell non-Hodgkin lymphomas and B lymphoblastic leukemias are positive for CD22. |
| 1910 |
CD23 (BU38) |
FCER2 |
88342 |
CD23 antigen is a 45-60 kDa membrane glycoprotein identified as a low affinity receptor for IgE production as well as a receptor for lymphocyte growth factor. CD23 is found in some mature B-cell lymphomas and in Reed-Sternberg cells in Hodgkin disease. Follicular dendritic cells and some activated B-cells within germinal centers express CD23 in high density and mantle zone B-cells are stained weakly. The majority of chronic lymphocytic leukemias/small lymphocytic lymphomas are CD23 positive, whereas mantle cell lymphomas are generally negative, so this marker is useful when applied with other markers to separate the small cell lymphomas. Precursor B and T lymphomas, myeloid neoplasms, and mature T-cell lymphomas are CD23 negative and other small cell lymphomas are occasionally positive. CD23 is also positive on activated mature B-cells expressing IgM or IgD, monocytes/ macrophages, follicular dendritic cells, T-cell subsets, eosinophils, Langerhans cells and small lymphocytic lymphoma/chronic lymphocytic leukemia (SLL/CLL). |
| 1911 |
CD25 (4C9) |
IL2RA |
88342 |
CD25 antigen, the alpha subunit of interleukin-2 receptor, is a single-chain glycoprotein with a molecular weight of 55 kD. Following the activation of T cells interleukin-2 (IL-2) is rapidly synthesized and secreted. In response to this a subpopulation of T cells expresses high affinity receptors for IL-2. These cells proliferate, expanding the T cell population which is capable of mediating helper, suppressor and cytotoxic functions. IL-2 receptor is not exclusively found on T cells, and is reported to be expressed on HTLV-transformed T and B cells, EBV-transformed B cells, myeloid precursors and oligodendrocytes. It is absent on thymocytes, resting T cells, non-activated B cells and null cells. IL-2 receptor expression is reported to be associated with inflammatory and malignant conditions, lymphoid neoplasia, auto-immune diseases and allograft rejection. |
| 1912 |
CD3 (2GV6) |
|
88342 |
CD3 (2GV6) is a rabbit monoclonal antibody produced against a synthetic peptide from the carboxy terminal region of the CD3 epsilon chain. CD3 epsilon chain is expressed in T lymphocytes, natural killer (NK) cells, and T-cell and NK-cell neoplasms. The CD3 staining is located primarily in the membrane of mature T-cells; however, it can also be found in the cytoplasm of pro-thymocytes and NK cells. |
| 1913 |
CD30 (Ber-H2) |
Ki-1 antigen |
88342 |
The anti-CD30 (Ber-H2) antibody is a mouse monoclonal antibody produced against a membrane bound glycoprotein that has a molecular mass of 105-120 kD. CD30 is a member of the tumor necrosis factor superfamily which when activated results in the signaling for antiapoptotic pathways allowing for cell proliferation. CD30 antigen is expressed in mononuclear Hodgkin cells and multinucleated Reed Sternberg cells of Hodgkin lymphoma as well as on anaplastic large cell lymphomas. This antibody variably produces membranous, cytoplasmic, and Golgi staining of both lymphoma cells and of scattered large activated B cells and T cells in lymph nodes, spleen, tonsil, and thymus. This antibody may also stain a small proportion of plasma cells. |
| 1914 |
CD30 (JCM182) |
Ki-1 antigen |
88342 |
The CD30 antigen is a single chain glycoprotein with a molecular weight of 120 kD. CD30 antigen is known to act as a receptor for a cytokine ligand, CD30L, and may also play a role in the regulation of cellular growth and transformation. CD30 antigen is reported to be expressed on the surface of multinucleated Reed Sternberg cells, mononuclear Hodgkin's cells and in the majority of anaplastic large cell lymphomas. The CD30 antigen is expressed in non-Hodgkin's lymphoma and virally transformed cells, eg EBV-transformed B cells. |
| 1915 |
CD31 (JC/70A) |
PECAM-1, platelet/endothelial cell adhesion molecule 1 |
88342 |
The antibody primarily labels endothelial cells, and is a useful tool for the identification of benign and malignant vascular disorders, including angiosarcomas. In addition, the antibody is valuable for the labelling of vessels when determining angiogenesis in several types of tumors. CD31 is a single chain type 1 transmembrane protein with a molecular mass of approximately 135 kDa, belonging to the immunoglobulin superfamily. In human serum, alternatively spliced versions of CD31 have been detected, including a form apparently lacking a transmembrane domain, but including the cytoplasmic tail. CD31 binds in both a homophilic and heterophilic manner. The heterophilic ligands include heparan sulfate glycosaminoglycans, heparin, and the integrin avb3. CD31 plays a role in adhesive interactions between adjacent endothelial cells as well as between leucocytes and endothelial cells. The ligation of CD31 to the surfaces of leucocytes results in upregulation of the functional leucocyte integrins, and the leucocyte diapedesis across the endothelium involves homophilic CD31 interactions. In addition, heterophilic CD31 interaction has a separate role in the migration of monocytes across the subendothelial basal lamina. CD31 is expressed on all continuous endothelia, including those of arteries, arterioles, venules, veins, and non-sinusoidal capillaries, but it is not expressed on discontinuous endothelium in e.g. splenic red pulp. In addition, CD31 is expressed diffusely on the surfaces of megakaryocytes, platelets, myeloid cells, natural killer cells, and some subsets of T cells, as well as on B-cell precursors. |
| 1916 |
CD33 (PWS44) |
SILEC3, gp67 |
88342 |
Clone PWS44 is recommended for the identification of human CD33 protein in normal and neoplastic tissues. In normal tissues, clone PWS44 detected the CD33 antigen in myeloid and myelomonocytic hemopoiesis and mature macrophages; cells of the erythroid and megakaryocytic series are negative. Some reactivity was observed in cytotrophoblasts and syncytiotrophoblasts of placenta. Except for dendritic cells and infiltrating macrophages, no staining was observed in other normal tissues evaluated (n=123). |
| 1917 |
CD34 (QBEnd/10) |
Hematopoietic Progenitor Cell Antigen CD34 |
88342 |
CD34 is a cell surface glycophosphoprotein expressed on human hematopoietic progenitor cells and can be used for identifying blast cells. CD34 is a marker for vascular endothelial cells and has been shown in literature to be highly sensitive for angiosarcomas and Kaposi’s sarcomas. In addition, CD34 is expressed in soft tissue tumors such as gastrointestinal stromal tumors (GIST). |
| 1918 |
CD35 (EP197) |
C3b receptor (C3bR), C4bR, Complement Receptor type 1 (CR1), Immune Adherence Receptor |
88342 |
CD35 is a type 1 single-chain cell surface membrane glycoprotein with molecular mass polymorphism due to differences in the number of short consensus repeats (SCRs) in the extracellular region and variation in glycosylation (190 kDa, 23 SCRs; 220 kDa, 30 SCRs; 250 kDa, 37 SCRs; 280 kDa, 44 SCRs). CD35 is expressed on erythrocytes, monocytes, neutrophils, eosinophils, B lymphocytes, and 10-15% of T lymphocytes. The protein is also found on follicular glomerular podocytes, dendritic cells and some astrocytes. CD35 is a receptor for C3b and C4b bound to immune complexes and functions as a cofactor for the specific proteolytic cleavage of C3b and C4b by the plasma serine protease, factor I. CD35 limits complement activation and produces ligands for other complement receptors. The antibody may be a useful tool for characterization of histiocytic/dendritic cell neoplasms and follicular dendritic cell sarcomas. |
| 1919 |
CD38 (SP194) |
ADP-RIBOSYL CYCLASE, CYCLIC ADP-RIBOSE HYDROLASE |
|
CD38, also known as ADP ribosyl cyclase 1, is a marker expressed by many hematolymphoid elements, including hematopoietic stem cells, hematogones and subsets of lymphoid cells with enzymatic and adhesion molecule features. It is also a marker of activation with particularly strong expression in plasma cells. Expression is membranous and can be detected by flow cytometry where it has utility in quantitative assessment, but it can also be detected by IHC. Positive staining is seen in B and T-cell neoplasms including plasmablastic lymphoma, Burkitt lymphoma, high grade B-cell lymphoma with MYC and BCL2 rearrangement, lymphoplasmacytic lymphoma, T-lymphoblastic leukemia/lymphoma, NK/T cell leukemia, peripheral T-cell lymphomas, amongst others. The anti-CD38 monoclonal antibody daratumumab is used therapeutically in multiple myeloma. It has also been used as a prognostic marker, with CD38 expression in chronic lymphocytic leukemia or hairy cell leukemia being associated with a more aggressive clinical course. CD38 can be seen on some subtypes of carcinoma and melanoma, prostate carcinoma or glioma. |
| 1920 |
CD4 (SP35) |
T-Cell Surface Antigen T4/Leu-3 |
88342 |
CD4 is a single chain transmembrane glycoprotein found on the helper-inducer T-cells, representing approximately 45% of mature peripheral blood T-cell lymphocytes. It is also present on about 80% of thymocytes as well as on some monocytes. B-cells do not express CD4. CD4 acts as a co-receptor for the T-cell receptor (TCR) and transduces the TCR signal following interaction with an antigen presenting cell. Anti-CD4 can be used as part of a panel of antibodies to classify T-cell disorders including T cell lymphomas and to differentiate between helper t cells and killer cells. |
| 1921 |
CD43 (MT1) |
Leukosialin, gpL115, sialophorin |
88342 |
CD43 is expressed, typically at high levels, on all leukocytes except most resting B lymphocytes. The expression on platelets is weak. CD43 is rapidly lost from lymphocyte and neutrophil surface by proteolytic shedding after activation with various stimuli. Although normal small B lymphocytes are negative for CD43, most low-grade B-cell lymphomas are positive. However, hairy cell leukemia, MALT lymphoma, and follicle center cell lymphomas are generally negative for CD43. In a study of 28 extramedullary myeloid tumors, all were intensely positive for CD43, irrespective of the differentiation of the myeloid cells. |
| 1922 |
CD44 (DF1-485) |
CD44s, ECMRIII, Hermes antigen, homing-associated cell adhesion molecule (H-CAM), and Pgp-1 |
88342 |
CD44 is a type I transmembrane adhesion molecule with a molecular mass of 85-90 kDa. It is a glycoprotein with extensive O-linked glycosylation and 6 potential N-linked glycosylation sites. A portion of the N-terminal domain of CD44 shows homology with a part of cartilage proteoglycan core and link proteins. CD44 is a cell surface receptor for hyaluronate suggesting a role in the regulation of cell and cell-substrate interactions as well as cell migration. CD44 is expressed on a wide variety of cells. In the hematopoietic system it is present on monocytes, granulocytes, erythrocytes, B cells and mature T cells. Outside the hematopoietic system it is expressed on epithelial cells, fibroblasts, skeletal muscle, central nervous system white matter, and a wide variety of tumors. CD44 is also known as CD44s, ECMRIII, Hermes antigen, homing-associated cell adhesion molecule (H-CAM), and Pgp-1. |
| 1923 |
CD45 (2B11+PD7/26) |
Leucocyte Common Antigen (LCA), T200, Ly-5 |
88342 |
CD45 is a transmembrane glycoprotein expressed on most nucleated cells of haematopoietic origin. CD45, encoded by a single gene mapped to chromosome 1, has various isoforms based on differential splicing of exons 4, 5 and 6. On human leucocytes, five different isoforms of CD45, named ABC, AB, BC, B and 0, have been identified. These isoforms are recognized by CD45RA, CD45RB, CD45RC and CD45R0 antibodies. The isoforms range in Mr from 180 000 to 220 000. All the CD45 isoforms share the same intracellular segment, which has been shown to have tyrosine phosphatase activity. Various leucocytes express characteristic CD45 isoforms, thus T cells express CD45 isoforms corresponding to their development and activation, B cells predominantly express the ABC isoform, and monocytes and dendritic cells predominantly express the B and 0 isoforms. Granulocytes principally express only the B and 0 isoforms. In an effort to promote standardization of diagnostic immunohistochemistry across laboratories, international multi-institutional groups have published a variety of best practices based on expert consensus recommendations. Guidelines published by the NordiQC proficiency testing consortium has provided recommendations for appropriate titration of CD45 immunohistochemistry. |
| 1924 |
CD5 (SP19) |
LEU1 |
88342 |
CD5 is a T-cell marker that also reacts with a range of neoplastic B-cells, e.g. B-cell chronic lymphocytic leukemia (B-CLL), B-cell small lymphocytic lymphoma (B-SLL), and mantle cell lymphoma. CD5 is expressed in T lymphocyte subsets and is modulated during cellular activation. CD5 does not react with granulocytes or monocytes. |
| 1925 |
CD56 (MRQ-42) |
Neural cell adhesion molecule (NCAM) |
88342 |
CD56, known as neural cell adhesion molecule (NCAM), was originally identified in the nervous system and belongs to a group of cell adhesion molecules including cadherins, selectins, and integrins. Anti-CD56 recognizes two proteins of the NCAM, the basic molecule expressed on most neuroectodermally-derived cell lines, tissues and neoplasms (e.g. neuroblastomas, small cell carcinomas). It is also expressed on some mesodermally-derived tumors (rhabdomyosarcoma). Furthermore, anti-CD56 has found great utility in the recognition of NK cell and NK/T-cell lymphomas. It has been shown that 71% of myelomas are positive for anti-CD56 as well. It also offers higher sensitivity in the diagnosis of small cell carcinoma than anti-chromogranin and anti-synaptophysin. Light staining of smooth muscle elements may be seen. |
| 1926 |
CD57 (NK-1) |
HNK-1, human natural killer-1 |
88342 |
CD57, also known as HNK-1 (human natural killer-1), is a cell surface carbohydrate epitope expressed on terminally differentiated T-cells and subsets of natural killer (NK) cells. It has also been identified on cells of neural crest origin. Anti-CD57 is often used to visualize the non-neoplastic bystander T-cells that may form rosettes around the neoplastic lymphocyte-predominant (LP) cells in nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) |
| 1927 |
CD61 (2f2) |
GPIIIa |
88342 |
Clone 2f2 detects the CD61 antigen in megakaryocytes and platelets. It is recommended for use in detecting CD61 protein expression in a variety of normal and neoplastic tissues. |
| 1928 |
CD68 (KP-1) |
Macrosialin |
88342 |
CD68 is a monocyte/macrophage marker useful in the diagnosis of myeloid sarcoma, histiocytic sarcoma, and acute myeloid leukemia. Several reagents exist including KP-1 and PG-M1. The latter has been reported by several groups to be more monocyte/macrophage restricted than KP-1. Therefore, these two cones may have different diagnostic utility. For example, KP-1 is a more sensitive marker for acute myeloid leukemia (AML) and, in particular, myeloid sarcoma than PGM-1. Both of these clones are well-characterized in the literature and widely used. In an effort to promote standardization of diagnostic immunohistochemistry across laboratories, international multi-institutional groups have published a variety of best practices based on expert consensus recommendations. Guidelines published by the NordiQC proficiency testing consortium has provided recommendations for appropriate titration of CD68 immunohistochemistry. |
| 1929 |
CD68 (PG-M1) |
Macrosialin |
88342 |
CD68 is a highly glycosylated lysosomal membrane protein with an Mr of 110 000. The CD68 protein belongs to a family of lysosomal glycoprotein (LGP)/plasma membrane shuttling proteins that play a role in endocytosis and/or lysosomal trafficking. CD68 is expressed strongly in cytoplasmic granules, and weakly on the surface of macrophages, monocytes, neutrophils, basophils and NK-cells. Additionally, CD68 is expressed by approximately 40% of peripheral blood B cells and is weakly expressed in 50% of B-cell type acute lymphoblastic leukaemia (B-ALL) cells. CD68 can also be found in the cytoplasm of non-haematopoietic tissues, especially the liver, and renal glomeruli and tubules. Unlike many other CD leucocyte antigens, the CD68 molecule is antigenically very heterogenous, and different antibodies to CD68 show different cellular reactivities. |
| 1930 |
CD7 (SP94) |
Tp41 |
88342 |
The CD7 molecule is a membrane-bound glycoprotein of 40 kDa, and is the earliest Tcell specific antigen to be expressed in lymphocytes. CD7 is expressed in the majority of thymocytes, peripheral blood T-cells and natural killer cells. Used in combination with CD4, CD7 is useful for differentiating mycosis fungoides and memory T-cells. |
| 1931 |
CD71 (10F11) |
Transferrin receptor-1 |
88342 |
CD71 (transferrin receptor-1) is an integral membrane glycoprotein that mediates cellular uptake of transferrin-iron complexes. CD71 has been found to be highly expressed on placental syncytiotrophoblasts, myocytes, basal keratinocytes, hepatocytes, endocrine pancreas, spermatocytes, and erythroid precursors. Among erythroid precursors, CD71 expression is highest in the early and intermediate normoblast phase, and then decreases through the reticulocyte phase. Eventually, CD71 expression is lost in mature erythrocytes. The high level of CD71 expression within erythroid precursors and absent expression in mature erythrocytes makes CD71 an ideal marker for evaluating erythroid elements in bone marrow. |
| 1932 |
CD79a (JCB117) |
Ig-α |
88342 |
The antibody labels B cells and is a useful tool for the identification of B-cell neoplasms of all maturation stages. CD79 is a disulphide-linked transmembrane heterodimer with a molecular mass of 82-95 kDa belonging to the immunoglobulin superfamily. It comprises the two glycoproteins, CD79α with a molecular mass of 40-45 kDa, and CD79β with a molecular mass of 37 kDa. CD79 is non-covalently associated with surface Ig, forming the B-cell receptor complex, which is required for antigen recognition. CD79 is essential for efficient surface expression of the B-cell receptor, and is also necessary for signal transmission into the cytoplasm following antigen-binding to surface Ig. The cytoplasmic portion of CD79α and CD79β contains several kinases. Phosphorylation signals via these kinases result in B-cell activation, differentiation and, in some cases, apoptosis. The expression of CD79 is largely restricted to B-linage cells, but CD79α is coexpressed with CD3 in a proportion of T-lymphoblastic leukaemia/lymphoma. In precursor B cells, the CD79 protein chains are already expressed in the cytoplasm (CyCD79). Surface expression of CD79 begins at the pro-B cell stage and persists throughout the B-cell differentiation. CD79α is more strongly expressed by B cells in the follicular mantle zone than by germinal center B cells, suggesting that activation of mature B cells downregulates CD79 expression. CD79 expression ceases around the onset of plasma cell differentiation, with only a proportion of plasma cells containing CD79. |
| 1933 |
CD8 (SP57) |
|
88342 |
CD8 is a heterodimeric, disulphide linked, transmembrane glycoprotein found on the cytotoxic-suppressor T cell subset representing 30-35% of peripheral blood T cell lymphocytes, but not on B cell lymphocytes. CD8 is also present on 80% of thymocytes, at a lower level on approximately 30-50% of natural killer cells, and in a subpopulation of bone marrow cells. CD8 acts as a coreceptor for the T cell receptor and interacts directly with MHC class I molecules during T cell activation. Anti-CD8 can be used as part of a panel of antibodies to classify T cell disorders, including T cell lymphomas, and to differentiate between helper and cytotoxic T cells. |
| 1934 |
CD99 (EPR3097Y) |
MIC2 |
88342 |
CD99, as detected with a variety of antibodies, is expressed by almost all Ewings sarcoma and primitive peripheral neuroectodermal tumors (ES/PNET) and demonstrates strong and diffuse membranous staining. Other tumors that may show CD99 expression include neuroendocrine carcinomas, mesenchymal chondrosarcomas, solitary fibrous tumors, synovial sarcomas, vascular tumors, small round blue cell tumors, lymphoblastic lymphoma, acute myeloid leukemia, and myeloid sarcoma. However, strong and diffuse membranous reactivity for CD99 favors ES/PNET over the other diagnostic considerations. The other CD99+ tumors usually show cytoplasmic and more heterogeneous staining. Therefore, when making a final diagnostic interpretation, CD99 must be considered in a panel with other antibodies. |
| 1935 |
CDX-2 (EPR2764Y) |
CDX2, Caudal type homeobox 2 |
88342 |
CDX-2 is a caudal-related homeobox transcription factor whose expression in the adult is normally present in the gastrointestinal (GI) epithelium. It is implicated in the development and maintenance of the intestinal mucosa. This protein is expressed immunohistochemically in the nuclei of normal GI epithelium.1 CDX-2 protein expression has been seen in GI carcinomas. Anti-CDX-2 has been useful to establish GI origin of metastatic adenocarcinomas and carcinoids and is especially useful to distinguish metastatic colorectal adenocarcinoma from lung adenocarcinoma. However, mucinous carcinomas of the ovary also stain positively with this antibody, which limits the usefulness of this marker in the distinction of metastatic colorectal adenocarcinoma versus mucinous carcinoma of the ovary. |
| 1936 |
CEA (EPCEAR7) |
Carcinoembryonic Antigen |
88342 |
Carcinoembryonic antigen (CEA) is a 180-kDA cell surface glycoprotein overexpressed in 90% of gastrointestinal malignancies, including colon, gastric, rectal, and pancreatic tumors, 70% of lung cancers, and about 50% of breast cancers. |
| 1937 |
Chromogranin (LK2H10) |
CHGA |
88342 |
Chromogranin A is present in secretory granules of endocrine cells. Chromogranin A is a marker for neuroendocrine differentiation and antibodies to chromogranin A are a useful tool for the identification of neuroendocrine-derived tumors. Chromogranin A is a protein prohormone with a molecular mass of 48 kDa. The gene encoding the 439 amino acids protein is localized on chromosome 14. Potentially biologically active peptides derived from chromogranin A are; vasostatins (aa 1-17/113), chromostatin (aa 124-143), chromacins (aa 173-194), pancreastatin (aa 243-294), WE-14 (aa 316-329), catestatin (aa 344-364), parastatin (aa 347-419) and GE-25 (aa 367-391). Chromogranin A was first isolated from chromaffin cells in the adrenal medulla but was later found to be present in secretory granules in cells of most neuroendocrine organs. Since then it has been used as an important broad spectrum histochemical marker for the identification of neuroendocrine cells and tumors. |
| 1938 |
Chymotrypsin (10-104.10) |
alpha-chymar ophth, chymotest, enzeon, quimar |
88342 |
Chymotrypsin is a serine endopeptidase produced by the acinar cells of the pancreas. It is expressed within the secretory granules on the apical aspect of acinar cells. Chymotrypsin is one of the commonly used markers for identifying cells with pancreatic acinar origin. Pancreatic neuroendocrine tumors (pancreatic NETs or PNET) develop from the abnormal growth of endocrine (hormone-producing) cells in the pancreas. It accounts for less than 5% of all pancreatic tumors. PNETs and acinar cell carcinoma of the pancreas differ considerably in both biological behavior and prognosis. Accurate distinction between PNETs and acinar cell carcinoma is of great importance but often challenging. A panel of IHC markers is routinely used in combination with histologic features of the tumors for the differential diagnosis. PNET cells do not produce chymotrypsin and thus stain negative with anti-chymotrypsin by IHC. |
| 1939 |
CK 19 (A53-B/A2) |
Cytokeratin 19 |
88342 |
Anti-cytokeratin 19 reacts with epithelia and epithelial malignancies including carcinomas of the colon, stomach, pancreas, biliary tract, liver, and breast. Anti-cytokeratin 19 is very useful in differentiation of hepatocellular carcinoma from intrahepatic cholangiocarcinoma, especially in a combination of cytokeratin 7, CAM5.2, Ber-EP4/MOC31, HepPar1 and TTF1. Another useful application is the identification of thyroid papillary carcinoma. |
| 1940 |
CK 20 (Ks20.8) |
Cytokeratin 20 |
88342 |
CK 20 belongs to the intermediate filament proteins, which create a cytoskeleton in almost all cells. In contrast to other intermediate filaments, cytokeratins (CKs) are made up of a highly complex multigene family of 40 to 68 kDa polypeptides. Twenty distinct CK polypeptides have been revealed in various human epithelial cells and their malignant counterparts. They can be divided into an acidic (type I) and a neutral-basic (type II) subfamily. CK 20, a 46 kDa protein, is less acidic than the other type I cytokeratins. CK 20 positivity (5-100% CK-20-positive tumor cells) has been reported in the vast majority of adenocarcinomas of the colon, mucinous ovarian tumors, transitional-cell and Merkel cell carcinomas, and frequently also in adenocarcinomas of the stomach (50%), bile system (75%), and pancreas (40%). Less than 2% of breast and lung adenocarcinomas and squamous cell carcinomas were positive, while adenocarcinomas of the ovary (non-mucinous) and endometrium, and renal cell and small cell carcinomas showed only scattered positive cells in some cases. |
| 1941 |
CK 5/6 (D5/16B4) |
Cytokeratine 5/6 |
88342 |
Cytokeratin 5/6 (CK 5/6) stain distinguishes epithelioid mesothelioma (CK5/6+ in 83%) from lung adenocarcinoma (CK5/6- in 85%), including in pleural effusions (CK5/6+ in 90% mesothelioma, 0% adenocarcinoma). Can be also used to distinguish breast usual ductal hyperplasia (UDH) and papillary lesions (mosaic-like pattern) from DCIS (usually negative, rarely diffusely positive) and to differentiate between cutaneous spindle squamous cell carcinoma (CK5/6+ in 100%) and superficial epithelioid sarcoma (rare focal positivity). Moreover, together with p63 positivity, it can identify squamous origin in poorly differentiated metastatic carcinomas (e.g., cervical). |
| 1942 |
CK 7 (OV-TL 12/30) |
Cytokeratin 7 |
88342 |
Cytokeratin 7 belongs to the intermediate filaments, which create a cytoskeleton in almost all eukaryotic cells. In contrast to other intermediate filaments, cytokeratins (CKs) are made up of a highly complex multigene family of polypeptides with molecular masses ranging from 40 to 68 kDa. CKs are generally held to belong to the most fundamental markers of epithelial differentiation, and until now, 20 distinct CK polypeptides have been revealed in various human epithelia. The CKs can be divided into an acidic type A (class I) and a neutral-basic type B (class II) subfamily. CK7, a 54 kDa protein, belongs to the neutral-basic type B subfamily, and its distribution is confined to glandular and transitional epithelia. In normal tissues, the antibody consistently labels a large number of simple-, complex- and transitional epithelia, including biliary and pancreatic ducts, lung alveoli, endometrium, distal convoluted tubules and collecting ducts of the kidney (simple epithelia), bronchial and bronchiolar epithelium, ducts of prostate, luminal cells of fallopian tube and endocervix, bronchial-, breast-, salivary-, sweat- and endocervical glands, placental trophoblasts (complex epithelia), and all cell layers of urothelium (transitional epithelium). Additionally, the antibody labels ovarian mesothelium and labelling has also been observed in luminal- and basal cells of the prostate and myoepithelial cells. Further, in frozen sections, the antibody has been shown to label the rete epithelium in the testis, epididymis epithelium, and the surface epithelium of the stomach and duodenum. Non-epithelial tissues, such as connective tissue, blood vessels, and lymphoid tissue, are negative with the antibody. |
| 1943 |
CK OSCAR (OSCAR) |
Pancytokeratin OSCAR |
88342 |
Cytokeratin (OSCAR) is a wide-spectrum cytokeratin. It stains cytokeratins present in normal and abnormal human tissues and has shown high sensitivity in the recognition of epithelial cells, making it a useful marker for identifying several types of carcinoma. Although it shows similar staining pattern as another widely used cytokeratin antibody, AE1/AE3 (a cocktail of two clones), it has the advantage of recognizing cytokeratin 8 and 18 that are missed by AE1/AE3. Cytokeratin18 is expressed in hepatoma and many other carcinomas. In fact, it is well known that some tumors such as hepatocellular and renal cell carcinomas are characteristically negative for AE1/AE3.Thus, OSCAR can be another choice of pan-keratin antibody to identify carcinomas in the context of undifferentiated malignancies. |
| 1944 |
CK8/18 (B22.1/B23.1) |
Cytokeratin 8 &18 |
88342 |
Cytokeratins 8 & 18 (CK 8 & 18) can be found in most simple epithelia, e.g. thyroid, female breast, gastrointestinal tract, and respiratory tract.1 Adenocarcinomas and most non-keratinizing squamous carcinomas will stain with anti-CK 8 & 18, but keratinizing squamous carcinomas will not. |
| 1945 |
Claudin-4 (3E2C1) |
Clostridium perfringens enterotoxin receptor |
88342 |
Claudin-4 (Clostridium perfringens enterotoxin receptor) is a tight junction protein encoded by the gene CLDN4. Claudin-4 has been shown to distinguish adenocarcinoma from malignant mesothelioma with 99% specificity in malignant effusions. Claudin-4 overexpression is observed in a wide variety of carcinomas, with varying prognostic effects. |
| 1946 |
CL-NOTCH1 (D3B8) |
Cleaved NOTCH1, Notch1 intracellular domain (NOTCH1-ICD) |
88342 |
NOTCH1 is a member of the NOTCH family of transmembrane proteins. Upon ligand binding, the intracellular domain is released by cleavage between the Gly1753 and Val1754 residues. Upon cleavage, the free cytoplasmic domain mediates downstream signaling including cell differentiation, proliferation and apoptosis programs. The NOTCH1 D3B8 antibody recognizes only the intracellular domain of NOTCH1 upon cleavage at Val1754 and does not recognize full-length NOTCH or NOTCH cleaved at other positions.1 |
| 1947 |
Clusterin (41d) |
Apolipoprotein J, glycoprotein III, SGP-2 |
88342 |
Clusterin is also known as apolipoprotein J, complement lysis inhibitor, gp80, glycoprotein III, SGP-2, SP 40-40, TRPM2 and T64. It is a ubiquitous multifunctional protein of 80kD comprised of two disulfide-linked subunits, alpha and beta, and is capable of interacting with a broad range of molecules. It is implicated in numerous biological processes including sperm maturation, lipid transport, and regulation of the complement cascade, membrane recycling, cell death, immune regulation, cell adhesion, and morphological transformation. In pathological conditions, it is an amyloid associated protein co-localizing with fibrillar deposits in systemic and localized amyloid disorders. In Alzheimer’s disease, clusterin is present in amyloid plaques and cerebrovascular deposits. In breast cancers, clusterin expression was found to correlate with tumour size. Clusterin is also implicated with endometrial cancers, myocardial infarction, renal diseases, and atherosclerosis. |
| 1948 |
CMV (DDG9,CCH2) |
Cytomegalovirus |
88342 |
Reacts with CMV immediate early antigen and early antigen. The antibody shows no cross-reaction with other herpesviruses or with adenovirus. Cytomegalovirus (CMV) is a common virus that infects people of all ages. In the United States, nearly one in three children are already infected with CMV by age 5 years. Over half of adults by age 40 have been infected with CMV. CMV persists for life and can reactivate. A person can also be reinfected with a different strain of the virus. Healthy individuals infected with CMV generally show no signs or symptoms. However, CMV infection can cause serious health problems for people with weakened immune systems (i.e. HIV, transplant, or medication), as well as fetuses in utero. |
| 1949 |
c-MYC (Y69) |
MRTL |
88342 |
c-MYC is a proto-oncogene that encodes the c-Myc protein, a transcription factor involved in cell proliferation. Abnormalities of c-MYC are found in many cancers and in many cases c-Myc is overexpressed as a result of translocations. Nearly 100% of Burkitt lymphomas and 5% to 8% of diffuse large B-cell lymphoma (DLBCL) harbor a c-MYC translocation. Furthermore, DLBCL with a c-MYC translocation exhibit a more aggressive clinical course and inferior response to chemotherapy when compared to DLBCL without translocations involving c-MYC. The immunohistochemical stain (IHC) for c-Myc may provide a cheaper and faster alternative to fluorescence in situ hybridization (FISH) in the detection of cases with c-MYC translocations, to assist in the diagnosis of Burkitt lymphoma, DLBCL and double hit B-cell lymphoma. |
| 1950 |
CXCL-13 (53610) |
BLC, BCA-1 |
88342 |
CXCL13 is a useful marker in the detection of angioimmunoblastic T cell lymphomas, and helps distinguish this entity from other T cell lymphomas. |
| 1951 |
CyclinD1 (SP4-R) |
PRAD-1, BCL1 |
88342 |
Cyclin D1 (PRAD-1, bcl-1) is one of the key cell cycle regulators, and functions in association with cdk4 and/or cdk6 by phosphorylating the Rb protein. Cyclin D1 is a putative proto-oncogene overexpressed in a wide variety of human neoplasms including mantle cell lymphomas (MCL). In addition, cyclin D1 positively regulates protein phosphorylation, mammary gland epithelial cell proliferation, and fat cell differentiation. In humans, the CCND1 gene encoding cyclin D1 is present on chromosome 11. ...Cyclin D1 is a cytoplasmic and nuclear protein that is synthesized during G1 phase and assembles with either cyclin-dependent kinase 4 (CDK4) or CDK6 in response to growth factor stimulation. D-type cyclin-CDK complexes act to inactivate the growth-suppressive function of the Rb protein through its phosphorylation, and titrate CDK inhibitors such as p21Cip1 and p27Kip1. Without growth factor-mediated stimulation, Cyclin D1 is unstable, and undergoes ubiquitin-mediated degradation, which is triggered by its phosphorylation. Cyclin D1 destabilization participates in G1/S phase arrest. The Cyclin D1 protein belongs to the highly conserved cyclin family, whose members are characterized by a dramatic periodicity in protein abundance throughout the cell cycle. Cyclins function as regulators of CDK kinases. Different cyclins exhibit distinct expression and degradation patterns which contribute to the temporal coordination of each mitotic event. Cyclin D1 forms a complex with and functions as a regulatory subunit of CDK4 or CDK6, whose activity is required for cell cycle G1/S transition. The Cyclin D1 protein has been shown to interact with tumor suppressor protein Rb and the expression of this gene is regulated positively by Rb. Mutations, amplification and overexpression of this gene, which alters cell cycle progression, are observed frequently in a variety of tumors and may contribute to tumorigenesis. Cyclin D1 has been successfully employed and is a promising tool for further studies in both cell cycle biology and cancer associated abnormalities. |
| 1952 |
D2-40 (D2-40) |
Lymphatic Endothelial Marker, PODOPLANIN, T1A-2 |
88342 |
The monoclonal antibody D2-40 recognizes podoplanin, a transmembrane mucoprotein that is expressed in lymphatic endothelium and lymphangiomas. This antibody stains the endothelium of lymph vessels but does not react with the endothelium of capillaries, arteries, and veins in formalin-fixed paraffin-embedded tissues. Therefore D2-40 is often used as a lymphatic marker for assessing lymphatic invasion. D2-40 staining has also been found in cells of mesothelial origin. |
| 1953 |
Desmin (D33) |
DES |
88342 |
Desmin labels smooth and striated muscle cells as well as mesothelial cells and is a useful aid for the classification of rhabdomyosarcoma, leiomyoma, and mesothelioma. Desmin belongs to the class III of intermediate filaments, constituting part of the cytoskeleton, and is the characteristic intermediate filament of all three types of muscle cells (skeletal, cardiac and smooth muscle). It is a 53-kDa protein encoded by nine exons of a gene located at 2q35. Desmin forms a cytoskeletal network across the muscle fiber bordering at the plasma and nuclear membrane and is particularly localized to the subplasmalemmal region and the Z-band. |
| 1954 |
DOG-1 (K9) |
ANO1 |
88342 |
DOG-1, a 986 amino acid protein of unknown function, is expressed predominantly on the plasma membrane of gastrointestinal stromal tumors (GISTs) and is rarely expressed in other soft tissue tumors, which, due to appearance, can be confused with GISTs. Reactivity for DOG-1 has been suggested to aid in the identification of GISTs, including Platelet-Derived Growth Factor Receptor Alpha mutants that fail to express KIT antigen. |
| 1955 |
DUX-4 (P4H2) |
Double homeobox 4 |
88342 |
Round cell sarcoma with CIC-DUX4 gene fusion is known as CIC-DUX4 sarcoma. CIC-DUX4 sarcoma is exceptionally rare and represents a genetically defined subtype of undifferentiated round cell sarcoma that morphologically resembles the Ewing sarcoma family of tumors. CIC-DUX4 Sarcoma harbor a recurrent translocation involving the CIC locus on 19q13 with 1 of 2 DUX4 loci (either 4q35 or 10q26.3). A recently published article demonstrated high sensitivity and specificity of DUX4 immunohistochemistry (IHC) in identifying CIC-DUX4 sarcoma. |
| 1956 |
EBNA-2 (PE2) |
EBV nuclear antigen 2 |
88342 |
The Epstein-Barr Virus (EBV), also called Human herpesvirus 4 (HHV-4), is a virus of the herpes family and is one of the most common viruses in humans. EBNA2 (EBV nuclear antigen 2) is one of the few genes of Epstein-Barr virus which are necessary for immortalization of human primary B lymphocytes. The EBNA2 protein acts as a transcriptional activator of several viral and cellular genes. |
| 1957 |
EBV-LMP1 (CS1,2,3,4) |
Epstein–Barr virus Latent Membrane Protein1 |
88342 |
The Epstein–Barr virus (EBV), also called human herpesvirus 4 (HHV-4), is one of eight known viruses in the herpes family, and is one of the most common viruses in humans. It is best known as the cause of infectious mononucleosis. It is also associated with particular forms of cancer, including a subset of Hodgkin lymphoma, Burkitt lymphoma, gastric cancer, nasopharyngeal carcinoma, and conditions associated with human immunodeficiency virus (HIV), such as hairy leukoplakia and central nervous system lymphomas. Other forms of immune suppression including for solid organ or hematopoietic stem cell transplant, iatrogenic therapy for autoimmune disease and age-related immunosenescence are also associated with an increased risk of EBV-related lymphoproliferative disorders. These malignancies are associated with latent EBV infection with the latency states, defined by different patterns of viral gene expression, varying based on the type of lymphoproliferative process as well as the host immune status. The non-coding RNAs EBER1/2 can be found in all latency states (0, I, IIa, IIb, and III). EBV latent membrane protein-1 (EBV LMP1) can be used to distinguish latency states IIa and III, with latency IIa being characteristic of EBV-associated forms of classic Hodgkin lymphoma. LMP-1 is of particular interest because of its potential role in oncogenesis, where it may mimic cellular CD40 signaling to activate NF-kB, Akt and other signaling pathways to promote growth, survival and metabolic remodeling. |
| 1958 |
E-Cadherin (36) |
CDH1 |
88342 |
E-cadherin is a calcium-regulated adhesion molecule expressed in most normal epithelial tissues. It is associated with gland formation, stratification, and epithelial polarization. Selective loss of E-cadherin can cause dedifferentiation and invasiveness in human carcinomas. Reduced expression has been observed in aggressive tumors of the esophagus, ovary, and stomach. |
| 1959 |
EMA (E29) |
Epithelial membrane antigen, MUC1 |
88342 |
EMA antibody labels epithelial cells in a wide variety of tissues and is a useful tool for the identification of neoplastic epithelia. Epithelial membrane antigen (EMA) belongs to a heterogenous population of human milk fat globule (HMFG), proteins. HMFG is a complex secretory product of mammary epithelium and EMA can be recovered from the aqueous phase of skimmed milk following extraction in chloroform and methanol. Besides in milk, these proteins are present in a variety of epithelia of both normal and neoplastic types. A number of monoclonal and polyclonal antisera have been raised against these molecules and anti-EMA has been extensively studied in a large number of neoplastic conditions, most often in conjunction with other antibodies. EMA is valuable as a marker in the detection of breast carcinoma metastases in histological sections of liver, lymph node, and bone marrow, and is useful for differentiating anaplastic carcinoma from malignant lymphomas, and for the recognition of spindle cell epithelial malignancies. |
| 1960 |
Enolase (BBS/NC/V1-H14) |
NSE, Enolase |
88342 |
Enolases (2-phospho-D-glycerate hydrolase) are glycolytic homo- or heterodimeric isoenzymes, which catalyse the interconversion of 2-phosphoglycerate and phosphoenolpyruvate. Three subunits, α (46 kDa), β (44 kDa) and γ (46 kDa), constitute the building blocks of the enolase molecules, and five forms (αα, ββ, γγ, αβ, and αγ) of the enzyme have been identified. The enolases are divided in three main groups according to their localization: non-neuronal enolase (NNE or α), muscle-specific enolase (MSE or β), and neuron-specific enolase (NSE or γ). |
| 1961 |
EP4-Ber (EA) (Ber-EP4) |
Epithelial Antigen |
88342 |
The antibody labels most epithelial cells and is a useful aid in the classification of adenocarcinoma. The antibody may also aid in the classification of esophageal carcinoma and classification of basal and squamous cell carcinomas of the skin. Epithelial antigen is a cell surface glycoprotein of unknown function. This epithelium-specific antigen is broadly distributed in epithelial cells and displays a highly conserved expression in carcinomas. As exceptions to the general expression in normal epithelia, adult hepatocytes, in contrast to fetal hepatocytes, parietal cells in gastric glands, and apical cells in squamous epithelia are negative. Epithelial antigen may rarely be present in mesotheliomas. It has been reported that epithelial antigen may play an important role as tumor-cell marker in lymph nodes from patients with esophageal carcinoma otherwise classified as node-negative. |
| 1962 |
ERG (EPR3864) |
Erythroblast transformation specific related gene |
88342 |
Defects in ERG are a cause of Ewing sarcoma (ES) [MIM:612219]. A highly malignant, metastatic, primitive small round cell tumor of bone and soft tissue that affects children and adolescents. It belongs to the Ewing sarcoma family of tumors, a group of morphologically heterogeneous neoplasms that share the same cytogenetic features. They are considered neural tumors derived from cells of the neural crest. Ewing sarcoma represents the less differentiated form of the tumors. |
| 1963 |
Estrogen Receptor (SP1) |
ER |
88360 |
Determination of ER status for all primary breast carcinomas was recommended by the National Institutes of Health (NIH) in 1979, to better determine appropriate therapy. In 1985, both the NIH and the American Cancer Society independently published reports in support of determining hormone receptor status as an aid in the management of breast cancer. In 1996, the American Society of Clinical Oncology, based upon the findings of their Tumor Marker Panel, recommended the determination of ER and PR status on all primary lesions and on metastases if the results would influence treatment planning. They also recommended using the ER and PR results for identification of patients most likely to benefit from endocrine adjuvant therapy and therapy for recurrent or metastatic disease. The Tumor Marker Panel also noted that ER and PR status may play a role in prognosis, but cautioned that they should be evaluated in conjunction with other clinical criteria, as ER and PR status alone were relatively weak predictors of long term relapse and breast cancer-related mortality. The 2020 update to the American Society of Clinical Oncology/College of American Pathologists guidelines on Estrogen and Progesterone testing placed additional emphasis on the importance of low level positivity (1-10% positive nuclei) for estrogen receptor staining. As available, though limited, data suggest cases with 1 to 10% positivity may benefit from endocrine therapy, the Expert Panel continues to recommend cases with as low as 1 to 10% positive staining be reported as positive with a recommended comment explaining the low level positive results.5 Tonsil tissue is recommended as a low level positive control for estrogen receptor, in addition to the normal endometrium high level positive control tissue. |
| 1964 |
FACTOR XIII A (AC-1A1) |
Activated fibrin stabilizing factor |
88342 |
Factor XIIIa has been identified in platelets, megakaryocytes, and fibroblast-like mesenchymal or histiocytic cells in the placenta, uterus, and prostate, monocytes and macrophages and dermal dendritic cells. Anti-factor XIIIa has been found to be useful in differentiating between dermatofibroma (almost all cases +), dermatofibrosarcoma protuberans (-/+) and desmoplastic malignant melanoma (-). Anti-factor XIIIa positivity is also seen in capillary hemangioblastoma, hemangioendothelioma, hemangiopericytoma, xanthogranuloma, xanthoma, hepatocellular carcinoma, glomus tumor, and meningioma. |
| 1965 |
Fascin (IM20) |
p55 |
88342 |
Human fascin is a highly conserved 55 kD actin-bundling protein which shares extensive sequence homology with sea urchin fascin and the Drosophila singed gene (sn) protein. Fascin, encoded by the human homolog for sn (hsn) gene, has been localized to microspikes and stress fibers of cultured cells where it is thought to be involved in the formation of microfilament bundles. Fascin staining can be used as a secondary stain to aid in the potential diagnosis of classic Hodgkin lymphoma, although the specificity of the stain may be limited in this setting compared to mimickers such as anaplastic large cell lymphoma. Nonetheless, it can be useful combined with other factors in challenging cases, and the absence of fascin staining may be helpful to better exclude classic Hodgkin lymphoma. |
| 1966 |
Fast-Slow Myosin |
Fast Myosin: Myosin-1, Myosin heavy chain 1 Slow Myosin: Myosin-7, Myosin heavy chain 7 |
88344 |
Actomyosin filaments represent the principal structural contractile components of muscle cell sarcomeres. Myosin is a molecular motor that converts chemical energy into movement. This is established by sliding of actin and myosin filaments over each other while hydrolysis of adenosine triphosphate (ATP) provides energy for this process. The myosin ATPase properties of different heavy chains isoforms is widely used as the main diagnostic method for fiber-type separation. Immunohistochemical double staining can substitute the ATPase stainings and be a powerful tool for general diagnostic purposes. Moreover, the double staining is more reliable for the detection and separation of different fiber types, particularly regarding the highly atrophic fibers and hybrid fibers. |
| 1967 |
FGFR-3 (B-9) |
Fibroblast Growth Factor Receptor 3, CD333 |
88342 |
The expression of FGFR3 is dysregulated in a subset of patients with plasma cell myeloma due to the translocation t(4;14)(p16;q32). It has been previously reported that approximately 75% of cases of plasma cell myeloma with t(4;14)(p16;q32) show positivity for FGFR3 by immunohistochemistry, and are associated with an adverse prognosis. Identification of FGFR3 expression in myeloma using immunohistochemistry is therefore strongly suggestive of the presence of t(4;14), although a negative immunohistochemical stain does not completely exclude the possibility of this translocation. |
| 1968 |
FH (J-13) |
Fumarate Hydratase |
88342 |
Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) syndrome is an autosomal disorder caused by germline mutation in the fumarate hydratase (FH) gene on chromosome 1q43. HLRCC associated RCC is often aggressive with metastatic disease in 50% of patients at presentation, and identification of HLRCC is important in managing the disease. Additionally, HLRCC syndrome-associated RCC has been recognized as a separate entity by the 2013 International Society of Urological Pathology Vancouver Classification of renal tumors and included in the WHO classification since 2016. FH is a ubiquitously expressed mitochondrial enzyme that catalyzes the reversible hydration of fumaric acid to yield l-malic acid during the Krebs cycle. Although the definite diagnostic approach is to sequence the FH gene, immunohistochemistry (IHC) staining for FH enzyme has also been demonstrated to be a highly specific method in identifying HLRCC-associated tumors with much lower cost. However, it should be noted that a variety of mutations in FH gene are associated with HLRCC and theoretically only the mutations affecting FH protein expression can be detected by IHC staining. We developed an in-house FH IHC and validated the test using confirmed cases of HLRCC, and typical RCC cases not associated with HLRCC. |
| 1969 |
FosB (5G4) |
AP-1 transcription factor subunit |
88342 |
FOSB is a member of the FOS gene family (FOS, FOSB, FOSL1 and FOSL2). These genes encode leucine zipper proteins that dimerize with proteins of the HUN family, forming the transcription factor complex AP-1.1,2 In this role, FOSB protein has been implicated as a regulator of cell proliferation, differentiation and transformation. Immunohistochemistry for FOSB has been shown to be useful in the diagnosis and classification of vascular neoplasms. Pseudomyogenic hemangioendothelioma (PHE, also known as epithelioid sarcoma-like hemangioendothelioma) is consistently positive for nuclear FOSB expression.3,4 Some cases of PHE show cytoplasmic expression in addition to nuclear staining. Mimics of PHE, including epithelioid sarcoma (ES) and Kaposi sarcoma (KS) have been reported to be negative for FOSB or show only weak nuclear staining in a minority of cells. Subsets of other vascular tumors, including epithelioid hemangioma are also positive for FOSB staining. |
| 1970 |
FOXL2 (EPR4837) |
Forkhead box L2 |
88342 |
Forkhead box L2 (FOXL2) is a member of the fork-head-winged-helix family of transcription factors. The Foxl2 gene is one of the earliest genes expressed during female gonadal development and is required for folliculogenesis. The FOXL2 is specifically expressed as a nuclear protein in eyelids and in fetal and adult ovarian follicular cells. The FOXL2 expression continues through female reproductive life in the granulosa cells of developing follicles and the cumulus oophorus of the preovulatory follicle. Recent studies have revealed FOXL2 expression in all types of ovarian sex cord-stromal tumors (SCSTs), with the exception of steroid cell tumors. The studies suggest that FOXL2 can be a useful marker for SCSTs diagnosis. Ovarian SCSTs are relative rare tumors and their diagnosis is often difficult to establish. Differentiation of SCSTs from other ovarian tumors (epithelial or germ cell tumor) is challenging requiring both morphologic features and a panel of immunohistochemical markers. We have developed a protocol for performing FOXL2 immunohistochemistry (IHC) staining and validated its use in aiding the diagnosis of STSCs such as granulosa cell tumor, thecoma-fibroma and sertoli-leydig cell tumor. |
| 1971 |
FSH (C10) |
Follicle stimulating hormone |
88342 |
FSH antibody labels follicle stimulating hormone in normal and neoplastic tissue. The antibody labels gonadotropic cells of the pituitary and is useful in the classification of pituitary adenomas and in the differential diagnosis of primary and metastatic tumors of the pituitary. |
| 1972 |
Gastrin (P) |
GAST |
88342 |
Gastrin is a peptide hormone secreted by G cells that stimulates secretion of HCl by parietal cells in the pyloric antrum of the stomach, duodenum, and pancreas. It also increases gastric motility. Gastrinomas are pancreatic islet cell tumors that hyper-secrete gastrin causing peptic ulcer disease and diarrhea. Gastrinomas are the defining tumor of Zollinger-Ellison syndrome and are one component of multiple endocrine neoplasia type 1 (MEN1) syndrome. |
| 1973 |
GATA3 (L50-823) |
GATA Binding Protein 3 |
88342 |
Studies have shown GATA-3 orchestrates gene expression profiles during embryogenesis of a variety of human tissues, including hematopoietic cells, skin, kidney, mammary gland, and the central nervous system. Among several other roles, GATA-3 has recently been identified as a key player of luminal cell differentiation in the mammary gland. GATA-3 appears to control a set of genes involved in the differentiation and proliferation of breast cancer. The expression of GATA-3 has a strong association with the expression of estrogen receptor-alpha (ER) in breast cancer, and there is mounting evidence that GATA-3 can be used as a clinical marker to determine response to hormonal therapy and to refine the prognosis of breast cancer patients. GATA-3 has also been shown to be a novel marker for bladder cancer. In one study, GATA-3 stained 67% of 308 urothelial carcinomas, but none for prostate or renal carcinomas. |
| 1974 |
GCET1 (RAM341) |
Centerin, Seprin A9, SERPINA11, SERPINA11b, SERPINA9, Serine proteinase inhibitor A11, Germinal center B cell expressed transcript 1 protein |
88342 |
Germinal center (GC) B cell-expressed transcript 1 (GCET1) is a molecule that belongs to the family of serine-protease inhibitors or serpins. Expression of GCET-1 has been found in GC B cells and GC B cell-derived malignancies but not in resting or activated peripheral blood B cells. Thus GCET1 may be a potential marker for identification of GC B cell-derived lymphomas. In addition, the GCET1 positive diffuse large B-cell lymphomas (DLBCL) have been associated with a more favorable prognosis. GCET1 may also have some prognostic value for DLBCL. |
| 1975 |
GFAP (P) |
Glial fibrillary acidic protein |
88342 |
Glial fibrillary acidic protein (GFAP) is the principal intermediate filament of mature astrocytes, and the antibody is a useful tool for the identification of astrocytes in the central nervous system (CNS) under normal and pathological conditions. GFAP is a 50 kDa intracytoplasmic filamentous protein that constitutes a portion of the cytoskeleton in astro-cytes, and it has proved to be the most specific marker for cells of astrocytic origin. In the central rod domain of the molecule, GFAP shares considerable structural homology with the other intermediate filaments. Functionally, GFAP is thought to be important in astrocyte motility and shape by providing structural stability to astrocytic processes. Following injury to the human CNS caused by trauma, genetic disorders, or chemicals, astrocytes proliferate and show extensive hypertrophy of the cell body and processes, and GFAP is markedly upregulated. In contrast, with increasing astrocyte malignancy, there is a progressive loss of GFAP production. Thus, malignant astrocytomas have fewer tumor cells that stain positively and intensely for GFAP than do less malignant astrocytomas and normal brain specimens. Outside the CNS, sensitive detection methods may demonstrate GFAP in Schwann cells, enteric glia cells, salivary gland neoplasms, and metastasizing renal carcinomas. Additionally, GFAP immunoreactivity has been demonstrated in epiglottic cartilage, pituicytes, immature oligodendrocytes, papillary meningiomas, and myoepithelial cells of the breast. GFAP shows 90-95% homology between species, and cross-reacts with GFAP in cat, dog, mouse, rat, cow, and sheep. |
| 1976 |
GFAP/Olig2 |
Glial Fibrillary Acidic Protein/ Oligodendrocyte transcription factor |
88344 |
Olig2, a basic helix-loop-helix (bHLH) transcription factor, is involved in oligodendroglial specification. Olig2 expression was restricted to glial tumors and nontumoral glia. It was higher in oligodendrogliomas when compared to astrocytomas. In addition, there is no olig2 expression in the non-glial tumors including neuroepithelial tumors, medulloblastomas, and non neuroepithelial tumors. Glial fibrillary acidic protein (GFAP) is an intermediate filament (IF) protein that is expressed by numerous cell types of the central nervous system (CNS) including astrocytes and ependymal cells during development. GFAP is a useful for distinguishing cells of astrocytic origin in the CNS. Gliomas are divided in astrocytomas and oligodendrogliomas according to their morphological features and presumed cells of origin. Double staining of GFAP and Olig2 has been reported to identified two phenotypically distinct tumor populations, Olig2+/GFAP- and Olig2-/GFAP+. In pure oligodendrogliomas, tumor cells were Olig2+/GFAP-. Both Olig2+/GFAP- and Olig2-/GFAP+ tumor populations were found in astrocytomas. Double staining of GFAP and Olig2 is useful to assist in distinction of glial vs neuronal origin in primary CNS tumors. |
| 1977 |
GH (P) |
hGH, growth hormone, somatotropin |
88342 |
Human growth hormone (hGH) is a polypeptide produced and secreted by somatotrophs of the anterior pituitary gland (adenohypophysis). Somatotrophs account for approximately 50% of all anterior pituitary cells. Positive immunohistochemical staining for hGH is suggestive of tissue of pituitary origin. No other cells are known to be capable of producing pituitary hormones. Pituitary tumors, such as pituitary adenomas, may express hGH. Other pituitary hormones may also be produced but their absence does not exclude the diagnosis of pituitary adenoma. |
| 1978 |
GLUT1 (EP141) |
Glucose transporter 1, SLC2A1 |
88342 |
Glucose transporter 1 (GLUT1), the most abundant isoform among the human glucose transporter family (GLUT 1-14), controls cellular glucose uptake and plays an essential role in energy metabolism. Immunohistochemistry (IHC) studies have shown that GLUT1 is presented in a variety of human tissue such as the colon, lung, stomach, esophagus, and breast. GLUT1 is also highly expressed in microvascular endothelia sites of blood-tissue barriers, such as in the central nervous system (CNS), retina, ciliary muscle, placenta and endoneurium of peripheral nerves. However, it is not found in the vasculature of normal skin and subcutis. Based on this characteristic tissue restriction, further studies on GLUT1 immunoreactivity in various vascular tumors and anomalies demonstrated that GLUT1 is highly specific for Juvenile or infantile hemangiomas (IH) and can be a reliable marker to differentiate IH from its histological mimics. IH are common, self-limiting, benign vascular tumors affecting 4-10% of infants. Unlike other vascular tumors or malformation, IH progression is highly predictable and always evolves through 3 stages: a rapidly proliferating stage of 8-12 months, followed by a prolonged involuting stage (1-12 years), and finally by a variable prominent late-stage fibrofatty residuum. Differentiating IH from its histological mimics is an important task regarding decisions with therapeutic approach and challenging due to the lack of specific markers. We have developed a protocol for performing GLUT-1 IHC staining and validated its use in the identification of IH from its histological mimics including vascular malformation and hemangioendotheliomas. |
| 1979 |
Glutamine Synth. (GS-6) |
GS |
88342 |
Glutamine synthetase, an enzyme that catalyzes the amination of glutamic acid to form glutamine, is found in mammals as an octamer of eight identical 45 kDa subunits. Glutamine synthetase activity has been shown to be a useful marker of astrocytes and an important differentiation feature in retina. Glutamine synthetase is also considered to be a key enzyme in the recycling of the neurotransmitter glutamate. |
| 1980 |
Glycophorin A (GA-R2) |
GYPA, CD235a |
88342 |
Glycophorin A is a sialoglycoprotein expressed in mature erythrocytes and nucleated erythroid precursors. Glycophorin A is a membrane protein carrying antigenic determinants for blood group specificities. The high sialic acid content of glycophorin A contributes to the generation of a net negative surface charge across erythrocyte membranes that minimizes interactions between red blood cells and prevents their aggregation. Staining for glycophorin A by immunohistochemistry is used to distinguish erythrocytes and erythroid precursors from other hematopoietic elements. |
| 1981 |
Glypican-3 (1G12) |
GPC3 |
88342 |
Glypican-3 (GPC3) is a glycosylphospatidyl inositol-anchored membrane protein, which may also be found in a secreted form. Recently, GPC3 was identified to be a useful tumor marker for the diagnosis of HCC, hepatoblastoma, melanoma, testicular germ cell tumors, and Wilms’ tumor. In patients with HCC, GPC3 was over expressed in neoplastic liver tissue and elevated in serum, but was undetectable in normal liver, benign liver, and the serum of healthy donors. GPC3 expression was also found to be higher in HCC liver tissue than in cirrhotic liver or liver with focal lesions such as dysplastic nodules and areas of hepatic adenoma (HA) with malignant transformation. In the context of testicular germ cell tumors, GPC3 expression is up-regulated in certain histologic subtypes, specifically yolk sac tumors and choriocarcinoma. A high level of GPC3 expression has also been found in some types of embryonal tumors, such as Wilms’ tumor and hepatoblastoma, with a low or undetectable expression in normal adjacent tissue. Together these studies indicate that GPC3 is an important tumor marker. |
| 1982 |
GPNMB |
Glycoprotein Nmb, HGFIN |
88342 |
Renal cell carcinoma (RCC) classification has historically been based on morphology, with clear cell RCC, papillary RCC, and chromophobe RCC. However, with the advances in molecular phenotyping classification of these tumors solely based on morphology has been challenging, in addition to the molecularly defined renal tumors. GPNMB (glycoprotein nonmetastatic B) is a melanosome-associated transmembrane glycoprotein and MITF/TFE3 transcriptional target and recently described as a specific marker for MiTF/TFE translocation-associated renal cell carcinomas and identification of renal tumors with TSC1/2MTOR alterations. Clinically, GPNMB helps to identify MiTF/TFE translocation-associated RCC and TSC1/2/MTOR alteration-associated renal tumors, distinguishing them from most conventional morphologic subtypes. |
| 1983 |
GranzymeB (GrB-7) |
GZMB |
88342 |
The granzyme B mouse monoclonal antibody reacts with the 33 kD human serine protease granzyme B. It does not react with human granzyme A. It is used as a marker for NK-cells and activated cytotoxic T-cells (CTL). This protease is localized in cytoplasmic granules and produces a granular staining pattern. Granzyme B is involved in target cell apoptosis during lymphocyte mediated cytotoxicity. Exocytosis of granzyme-containing granules in the cytoplasm of the target cell will lead to DNA fragmentation and apoptosis of the target cell. |
| 1984 |
H.Pylori (SP48) |
Helicobacter pylori |
88342 |
Helicobacter pylori (H. pylori) can exist in a number of locations: in the mucus, attached to epithelial cells, or inside of vacuoles in epithelial cells, where it produces adhesions that bind to membrane-associated lipids and carbohydrates in or on epithelial cells. The most reliable method for detecting H. pylori infection is a biopsy during endoscopy histologic examination and detection by immunohistochemistry. Helicobacter pylori is strongly associated with inflammation of the stomach and is also implicated in the development of gastric malignancy, peptic ulcers, and gastric lymphomas in humans. Immunohistochemical staining of H. pylori on the surface of gastric mucosa is a valuable tool for identification of H. pylori infections. |
| 1985 |
H3 K27me3 (C36B11) |
Tri-Methyl-Histone H3 Lys27 Wild Type |
88342 |
In most cells, histone 3 (H3) is trimethylated at lysine 27 (H3K27) as a consequence of the activity of the polycomb repressive complex (PRC2). It is designated “wild type”. In 70-90% of cases of malignant peripheral nerve sheet tumor (MPNST), constituents of the PRC2-SUZ12 and EED1 gain mutually exclusive mutations resulting in PRC2 inactivation and loss of H3K27me3. Immunohistochemical studies have demonstrated this loss of H3K27me3 in approximately 50% of total MPNST, a lower percentage of cases than the cases with mutations, probably due to the fact that both copies of either SUZ12 or EED1 need to be mutated in order for the PRC2 to be completely inactivated. Other soft tissue lesions have been investigated, but they appear to retain H3K27me3 by immunohistochemistry, which leads to the conclusion that loss of H3K27me3 by IHC may be useful in the diagnosis of MPNST. |
| 1986 |
H3 K27Mutant (EPR18040) |
H3K27M Mutant |
88342 |
Recurrent K27M mutations in histone 3 (H3) have been detected in midline high grade astrocytomas and have been associated with rapid fatal outcomes. Mutated cases tend to be diagnosed in children, in pontine and midline locations. |
| 1987 |
H3 K36M (RM193) |
Histone H3 (K36M Mutant Specific) |
88342 |
H3F3B is a member of the histone H3 family and is located on chromosome 17. Histone H3 K36M is expressed in the nuclei of the mononuclear cell population of H3F3B altered chondroblastoma. Somatic missense mutations in histone H3 genes are found in several pediatric brain and bone malignancies, among which ~90% of the chondroblastomas are identified with histone H3 K36M mutation (H3K36M). |
| 1988 |
H3G34W (RM263) |
Histone H3.3 G34W mutant |
88342 |
Nuclear chromatin is composed of nucleosomes, each containing a histone multimer wrapped by DNA. Mutations of histones, which can lead to alteration of gene expression and chromosomal stability, have been described in several types of neoplasms. The histone H3.3 G34W mutation has been reported in 90-95% of giant cell tumor of bone (GCTB), while other giant-cell rich lesions such as aneurysmal bone cysts (ABC) or osteosarcomas, which may mimic GCTB, have only rarely been reported to be positive for this mutation. Immunohistochemistry for H3.3 G34W is therefore useful in the differential diagnosis of giant-cell rich lesions. |
| 1989 |
HbcAG (P) |
Hepatitis B Core Antigen |
88342 |
Hepatitis B Virus Core Antigen (HBcAg) is part of the infectious virion containing an inner "core particle" enclosing the viral genome. The icosahedral core particle contains 180 or 240 copies of the core protein. HBcAg is one of the three major clinical antigens of hepatitis B virus but disappears early in the course of infection. The hepatitis B virus core antigen (HBcAg) is a highly immunogenic subviral particle and functions as both a T-cell-dependent and a T-cell-independent antigen. |
| 1990 |
HBME-1 (HBME-1) |
Mesothelial Cell, Hector Battifora mesothelial-1 |
88342 |
Hector Battifora mesothelial-1 (HBME-1) is a membrane antigen that exists in the microvilli of mesothelial cells and other epithelial cells. Anti-HBME-1 labels thyroid papillary carcinoma and follicular carcinoma but not normal thyroid making it a valuable marker for distinguishing thyroid malignacies from benign thyroid lesions. It has also been demonstrated to label mesothelial cells, both benign and malignant (malignant mesothelioma) and thus can aid in the identification of mesothelioma. |
| 1991 |
HbsAG (A10F1) |
Hepatitis B surface antigen |
88342 |
Hepatitis B surface antigen (HBsAg) contains the large, middle, and small proteins of the Hepatitis B virus (HBV). HBsAg is on the surface of HBV that is present in the bodily fluids and hepatocytes of infected individuals. It plays a key role in HBV’s infection of hepatocytic cells. |
| 1992 |
H-Caldesmon (h-CD) |
CALD1 |
88342 |
This antibody labels smooth muscle cells and is a useful aid in the classification of tumors with smooth muscle cell differentiation. Caldesmon is a developmentally regulated protein involved in smooth muscle and non-muscle contraction. Two closely related variants of human caldesmon have been identified. The h-caldesmon variant (120-150kDa) is predominantly expressed in smooth muscle and a subset of myoepithelial cells, whereas l-caldesmon (70-80kDa) is found in non-muscle tissue and cells. Neither of the two variants has been detected in skeletal muscle. |
| 1993 |
HCG (P) |
Human chorionic gonadotropin |
88342 |
Human chorionic gonadotropin (hCG) is a glycoprotein hormone composed of alpha and beta subunits, synthesized in syncytiotrophoblastic cells of placenta and in certain trophoblastic tumors such as choriocarcinoma. The alpha subunit of hCG is identical to the alpha subunit of LH, FSH, and TSH. The hCG beta subunit is unique and labels the cytoplasm of syncytiotrophoblastic cells and their tumors, as well as germ cell tumors of the ovaries, testes and extragonadal sites. |
| 1994 |
HEG1 (SKM9-2) |
HEART DEVELOPMENT PROTEIN WITH EGF-LIKE DOMAINS 1 |
88342 |
HEG homolog 1 (HEG1) is a novel calcium binding receptor protein that plays a role in endothelial cell interactions in the development of the vascular system and angiogenesis. HEG1 has been shown to be a useful marker in the diagnosis of mesothelioma, and has been shown to be a highly specific and sensitive marker of epithelioid mesothelioma, demonstrating a cytoplasmic and membranous pattern of staining versus non-small cell carcinoma, which is negative for HEG1. |
| 1995 |
Hemoglobin-A (SP212) |
HGB A |
88342 |
Hemoglobin belongs to the globin family of proteins and is involved in oxygen transport from the lung to the various peripheral tissues. Hemoglobin A is comprised of two alpha chains and two beta chains. Immunohistochemical localization of hemoglobin A serves as a marker for mature, anucleate erythrocytes as well as immature, nucleated erythroid precursors. In contrast, granulocytes, megakaryocytes, lymphocytes and plasma cells do not express hemoglobin A. |
| 1996 |
Hepatocyte (OCH1E5) |
HEP-PAR1 |
88342 |
Monoclonal antibody Hep Par 1 is an antigen that seems to be localized to the mitochondrial fraction of liver homogenates in both fetal and adult liver. It is conserved in most adult hepatocellular carcinomas including fibrolamellar variants. Hepatoblastomas also express Hep Par 1 with a pattern that is generally less intense in embryonal-type than in fetal-type hepatoblastomas, perhaps reflecting the degree of hepatocyte differentiation. Hep par 1 reacts with hepatocytes in routine formalin-fixed and paraffin-embedded tissue demonstrating diffuse cytoplasmic staining that is distinctly granular, and occasionally ring like. No canalicular accentuation is identified. There does not seem to be any zonal preference in normal liver, but immediately adjacent to tumors decreased labeling in compressed hepatocytes may be observed. No staining of bile duct epithelium or other non-parenchymal cells is seen. |
| 1997 |
HER2 (4B5) |
CERB2 |
88360 |
Breast cancer is the most common carcinoma occurring in women, and the second leading cause of cancer related death. In North America, a woman’s chance of contracting breast cancer is one in eight. Early detection and appropriate treatment therapies can significantly affect overall survival. Small tissue samples may be easily used in routine immunohistochemistry (IHC), making this technique, in combination with antibodies that detect antigens important for carcinoma interpretation, an effective tool for the pathologist in their diagnosis and prognosis of disease. One important marker in breast cancer today is c-erbB-2 oncoprotein (HER2). HER2 is an intracellular membrane protein detected in the cellular membrane. It is closely related to EGFR and, like EGFR, has tyrosine kinase activity. Gene amplification and the corresponding overexpression of c-erbB-2 has been found in a variety of tumors, including breast carcinomas. The therapeutic drug Herceptin has been shown to benefit some breast carcinoma patients by arresting, and in some cases reversing the growth of their cancer. The drug is a humanized monoclonal antibody that binds to HER2 protein on cancer cells. Thus only patients with HER-2/neu positive breast carcinomas should benefit from treatment with Herceptin. In vitro diagnostics for the determination of HER2 status in breast carcinomas are important to aid the clinician in determination of therapy with Herceptin. |
| 1998 |
Herpes (HSVI&II) (P) |
Herpes Simplex Virus I and II; HSV I & II |
88342 |
Herpes simplex viruses -- more commonly known as herpes -- are categorized into two types: herpes type 1 (HSV-1 or oral herpes) and herpes type 2 (HSV-2 or genital herpes). Most commonly, herpes type 1 causes sores around the mouth and lips (sometimes called fever blisters or cold sores). HSV-1 can cause genital herpes, but most cases of genital herpes are caused by herpes type 2. In HSV-2, the infected person may have sores around the genitals or rectum. Although HSV-2 sores may occur in other locations, they are usually are found below the waist. |
| 1999 |
HHV8 (13B10) |
Human Herpesvirus 8 |
88342 |
Human herpes virus type 8 (HHV-8) is the likely etiological agent of Kaposi’s sarcoma (KS). HHV-8 DNA sequences have been found in KS lesions and primary effusion lymphoma. Other conditions in which HHV-8 has been associated include multicentric Castleman’s disease, particularly in the setting of HIV infection. Therefore, detection of HHV-8 may be of use in diagnosis of these tumors. |
| 2000 |
HMB-45 (HMB-45) |
Anti-Melanoma |
88342 |
Metastatic amelanotic melanoma is often confused with a variety of poorly differentiated carcinomas, sarcomas, and large cell lymphomas. Primary spindle cell melanomas may also mimic spindle cell carcinomas and various types of mesenchymal neoplasms. HMB45 is described in literature to identify melanocyte differentiation antigen gp100. It reacts with fetal and neonatal melanocytes but not with normal adult melanocytes, junctional nevus cells but not with intradermal nevi, hence showing specificity for detection of melanocytic tumors. The panel of tumor markers most commonly used in conjunction with HMB45 for evaluation of melanoma includes S-100 protein, LCA, CEA, and EMA, as well as vimentin, an intermediate filament found in both melanomas and sarcomas. |
| 2001 |
HMGA2 (EP398) |
High Mobility Group AT-Hook, HMGIC |
88342 |
High mobility group A2 protein (HMGA2) is a non-histone, chromatin-associated molecule involved in maintenance and functional regulation of DNA, including the processes of replication, recombination, transcription, and DNA repair. HMGA2 is important during early embryogenesis and is highly expressed during oncogenesis. Studies have shown that HMGA2 increases cancer progression through the activation of several pathways. The diagnostic and prognostic value of HMGA2 stems from its overexpression in various tumor types, including lung, breast, and pleomorphic adenomas. |
| 2002 |
HPV (K1H8) |
human papillomavirus |
88342 |
Anti-human papillomavirus, clone K1H8 (anti-HPV) reacts with a non-conformational internal linear epitope of a major capsid protein of HPV-1, which is broadly expressed among the different HPV subtypes. Anti-HPV was found to be immunoreactive with paraffin sections of formalin-fixed HPV-infected tissues which were demonstrated by Southern blot hybridization to be infected with HPV type 6, 11, 16, 18, 31, 33, 42, 51, 52, 56 and 58. Positive immunostaining was largely confined to the nuclei of infected cells. Occasionally, the cytoplasm of koilocytotic cells was observed to be immunoreactive. |
| 2003 |
ICOS (D1K2T) |
CD278, Inducible co-stimulator |
88342 |
ICOS (Inducible Co-Stimulator, CD278) is a member of the CD28 family that regulates T cell activity and immune responses (1-2). The ICOS protein contains an extracellular IgV like domain, a transmembrane domain, and an intracellular domain with a YMFM motif (1-3). ICOS is primarily expressed on activated CD4+ and CD8+ T cells (1-2). Upon binding to its ligand, ICOS potentiates the T cell response to antigen through activation of the PI3K signaling pathway (1,3-4). In addition to enhancing T cell activation and proliferation, ICOS plays an important role in the regulation of T follicular helper (T-FH) cells (1, 5). Within T-cell non-Hodgkin lymphomas, ICOS (CD278) expression is frequently detected in angioimmunoblastic T-cell lymphomas and other peripheral T-cell lymphomas with a T-FH phenotype (6,7). |
| 2004 |
IDH-1 (H09) |
Isocitrate dehydrogenase 1 |
88342 |
Isocitrate dehydrogenase 1 (IDH1) is an important enzyme in the tricarboxylic acid cycle. It catalyzes the cytosolic oxidative decarboxylation of isocitrate, producing alpha-ketoglutarate and CO2 while converting NAD+ to NADH. High frequency of IDH1 mutations (ranging from 60%-80%) have been found in diffuse gliomas, World Health Organization (WHO) grades II and III of astrocytic and oligodendroglial lineages as well as in secondary glioblastoma WHO grade IV. In contrast, IDH1 mutations are rare in other brain tumors and nonneoplastic lesions with reactive glial proliferations. More than 90% of the IDH1 mutations involve a substitution of arginine by histidine at codon 132 (R132H). This amino acid change can be detected by IHC with a monoclonal antibody (anti-human IDH1R132H, clone H09). This antibody may be useful in distinguishing gliomas from reactive gliosis. |
| 2005 |
IDH2 (R172K) (14H7F11) |
Isocitrate Dehydrogenase (NADP(+)) 2 with R172K mutation |
88342 |
Mutations in isocitrate dehydrogenase 2 (IDH2) are identified in a subset of hematolymphoid neoplasms including acute myeloid leukemia and T-cell lymphomas of T follicular helper type with the R172K mutation being one of the most frequently identified mutations as well as other solid tumors including gliomas. Oncogenic mutations of either IDH1 or IDH2 at hotspot sites result in gain of function of the enzyme, production, and accumulation of the oncometabolite 2-hydroxyglutarate. Identifying such cases is of potential relevance for therapy, including as part of clinical trials, given the development of IDH2 specific inhibitor therapy. This antibody may also help in identifying residual/recurrent disease in some settings. |
| 2006 |
IgA (P) |
Immunoglobulin A |
88342 |
IgA is one of the most prevalent of the five classes of antibodies produced by the body. It is found in all secretions of the body and is the major antibody in the tears, saliva, and mucous membranes lining the intestines and bronchi. IgA combines with a protein in the mucosa and defends body surfaces by seeking out foreign microorganisms and triggering an antigen-antibody reaction. |
| 2007 |
IgD (EP173) |
Immunoglobulin D |
88342 |
Immunoglobulins function as the surface receptors in B lymphocytes and as the secretory products of plasma cells forming the humoral arm of the immune system. IgD is normally expressed on mantle zone B-cells. The identification of IgD on B-cell subsets can assist in assessing the architectural features of a lymphoid proliferation and aid in classification of lymphomas and myeloma. |
| 2008 |
IgG (RWP49) |
Immunoglobulin G |
88342 |
Immunoglobulins are heterodimeric proteins composed of two heavy chains and two light chains. Immunoglobulin G (IgG) is the most common type of antibody in serum and is normally produced by plasma cells to aid in the control of various types of pathogens. IgG antibodies are generated following class switching and maturation of the antibody response. From a diagnostic standpoint, IgG staining can be used in a variety of settings including to identify the heavy chain subtype of plasma cells associated with a plasma cell neoplasm or lymphoma with plasmacytic differentiation. In addition, there are four IgG subclasses (IgG1, IgG2, IgG3, IgG4). Of these, IgG4 usually constitutes a minor subset of total plasma cells (3-6%). An increased percentage of IgG4+ plasma cells (>40%) along with an increased absolute number of IgG4+ plasma cells is associated Ig4-related sclerosing disease and IgG4-related lymphadenopathy. While this must still be correlated with serum IgG4 levels, being able to accurately quantify the fraction of IgG+ plasma cells that are IgG4+ is one of the most important criteria for diagnosis. |
| 2009 |
IgG4 (HP6025) |
Immunoglobulin G4 |
88342 |
Early studies suggest that IgG4 as a serum and IHC tissue marker may be a sensitive diagnostic aide in AIP and a specific marker to differentiate this rare variant of chronic pancreatitis from usual type chronic pancreatitis due to alcoholism and gallstone obstruction and adenocarcinoma of the pancreatic head region, including pancreatic, common bile duct or ampullary adenocarcinomas. If so, preoperative diagnosis of this dreaded cause of false positive Whipple resections might be possible and unnecessary surgery might be avoided. |
| 2010 |
IgM (P) |
Immunoglobulin M |
88342 |
IgM normally constitutes about 10% of serum immunoglobulins. IgM antibody is prominent in early immune responses to most antigens and predominates in certain antibody responses such as 'natural' blood group antibodies. IgM (with IgD) is the major immunoglobulin expressed on the surface of B cells. The gene for the mu constant region contains four domains separated by short intervening sequences. Class specific anti immunoglobulin antibodies are useful for the characterization of malignant B cell proliferations. All but acute lymphocytic leukemias share either surface or intra cytoplasmic Ig with an isotypic restriction, which suggest the monoclonal nature of the cell population. Most of the chronic lymphocytic leukemias, non-Hodgkin lymphomas and Burkitt's lymphoma bear surface IgM, whereas plasmocytes from Waldenström's disease bear intracytoplasmic IgM. The other isotypes are less frequently found. On the other hand multiple myelomas are usually of the IgG or IgA type. Characterization of plasma cells in inflammatory conditions can be of use for the classification of intestinal inflammatory conditions such as inflammatory bowel disease and allergic conditions. In the latter a specific increase in the number of IgE plasma cells can be demonstrated. |
| 2011 |
Inhibin (alpha) (R1) |
Inhibin A, Inhibin alpha |
88342 |
Inhibin and activin are part of the transforming growth factor beta (TGF-ß) family of cytokines and are best known for their role in regulating follicle stimulating hormone (FSH) secretion, where inhibin inhibits and activin activates secretion. These protein regulators play a vital role in regulating FSH, which acts synergistically with luteinizing hormone (LH) in reproduction. Inhibins are found in the ovary (granulosa cells) and testis (sertoli cells), placenta, endometrium, brain, and adrenal gland. The antibody may be of value in the differentiation of adrenocortical tumors, placental and gestational trophoblastic lesions, and sex cord stromal tumors. |
| 2012 |
INI-1 (25/BAF47) |
SNF5, SMARCB1, BAF47 |
88342 |
The SMARCB1/INI-1 gene is a member of the ATP-dependent SWI/SNF chromatin-remodeling complex and has been considered as a tumor suppressor gene. All normal cells show nuclear expression of INI-1 protein. Biallelic inactivation of the INI-1 gene & absence of INI protein expression has been identified as a feature of malignant rhabdoid tumor by earlier studies. Loss of INI expression has also been found in renal medullary carcinoma & synovial sarcoma. Recently, loss of INI expression was reported in both conventional & proximal-type of epithelioid sarcoma. Here we validated an anti-INI-1 antibody for aiding diagnosis of epithelioid sarcoma. |
| 2013 |
INSM1 (MRQ70) |
Insulinoma-associated protein 1; zinc finger protein IA-1 |
88342 |
INSM1 (insulinoma-associated protein 1), also known as zinc-finger protein IA-1, is a developmentally regulated zinc-finger transcription factor. It localizes to the nucleus and is expressed in embryonic tissues undergoing neuroendocrine differentiation. INSM1 is not expressed in normal adult tissues but it can be found highly expressed in neuroendocrine tumors. INSM1 contains five Cys2-His2-type zinc-finger DNA binding domains and a prohormone domain. INSM1 has emerged as a robust immunohistochemical marker of neuroendocrine differentiation in normal and neoplastic human tissue, and is currently the only nuclear neuroendocrine marker available for use in diagnostic immunohistochemistry. |
| 2014 |
IRF8 (EPR20441) |
Interferon Regulatory Factor 8, ICSBP |
88342 |
Interferon Regulatory Factor 8 (IRF8) is a lineage-specific transcription factor of the interferon (IFN) regulatory factor (IRF) family that is critical for the production of monocytic and dendritic cell progenitors. Its expression highly correlates with aspirate blast count in acute monocytic leukemias (AMoL). Thus, IRF8 detection may serve as a clinically useful immunostain to diagnose and track AMoLs on bone marrow core biopsies. This could have potential utility particularly in the setting of poor aspiration and focal blast increase. |
| 2015 |
IRTA1 (EPR21961) |
FCRL4 |
88342 |
Immune receptor translocation-associated protein 1 (IRTA1), also known as Fc receptor–like 4 (FCRL4), is a member of a family of immunoglobulin-like proteins that mediate B-cell immune responses. In normal lymphoid tissues, IRTA1 is expressed in benign monocytoid B cells, some marginal zone cells, and intraepithelial B cells. IRTA1 expression, as determined by immunohistochemistry (IHC) using antibodies that are not commercially available, has been reported to be specific for MZL 67% to 73% of NMZLs and 93% of extranodal MALT lymphomas. Using RNA in situ hybridization (ISH), IRTA1 staining was found in 43% of NMZLs, 52% of extranodal MALT lymphomas, and 25% of SMZLs while only rare examples of other small B-cell neoplasms were positive. This validation study was carried out to assess performance of a newly commercially available rabbit monoclonal antibody, EPR21961. |
| 2016 |
Kappa (P) |
KAPPA LIGHT CHAINS |
88342 |
The human immunoglobulins basically consist of two identical heavy chains (Mr about 50 000) and two identical light chains (Mr about 20 000). The four chains are covalently linked together by disulphide bonds. The light chains are either kappa or lambda. The five immunoglobulins, IgA, IgD, IgE, IgG and IgM, differ regarding the heavy chains, and IgA and IgM also occur in polymeric forms. Individual B cells express either kappa or lambda light chains, but never both. In a polyclonal population the ratio of kappa to lambda bearing B cells is 2:1, and the occurrence of a mixture of kappa and lambda light chain-bearing cell types suggests polyclonality and a reactive or non-neoplastic proliferation of B cells. Diseases, such as multiple myeloma and B-cell lymphoma, are characterized by the proliferation of monoclonal neoplastic plasma cells producing only one type of light chain. Thus, the demonstration of a kappa or lambda light chain-restricted cell population is very useful in the histopathological diagnosis of these diseases. Primary AL (amyloid light-chain) amyloidosis is also a plasma cell disorder where the demonstration of monotypic kappa or lambda light chain in the amyloid deposits is diagnostically important and separates this disease from AA amyloidosis where immunoglobulin light chain deposits do not occur. In immunocytochemistry, the antibody labels plasma cells and related lymphoid cells containing kappa light chains, and it is a useful tool for the classification of patients with monoclonal gammopathies and amyloidosis. Additionally, the antibody may be used for distinguishing neoplastic monoclonal proliferation from reactive hyperplasia of B cells. Differential identification is aided by the results from a panel of antibodies. |
| 2017 |
KER 903 (34BE12) |
Cytokeratin 1/5/10/14, HMWCK |
88342 |
KER903 (34βE12) is specific for "high molecular weight" cytokeratins 1, 5, 10 and 14, corresponding to molecular weights 68, 58, 56.5 and 50 kDa, respectively, which are characteristically found in "complex" epithelium. The antibody reacts with all squamous and ductal epithelium as well as carcinomas such as squamous cell carcinoma and adenocarcinoma of ductal origin (e.g., breast, pancreas) but does not react with sarcoma, melanoma or lymphoma. This antibody reacts with benign small-acinar lesions of the prostate and has been shown to be useful as an adjunct in the identification of prostate carcinoma. |
| 2018 |
Ki 67 (30-9) |
Marker Of Proliferation Ki-67 |
88360 |
The Ki-67 antigen is a proliferation marker and is expressed by cells within the cell cycle but not in resting cells. Studies have shown this antigen to be expressed throughout S phase, G2 phase and M phase of the cell cycle but absent in G 0. It is a nuclear antigen and monoclonal antibodies have been developed that are suitable for use in paraffin embedded tissue sections. Assessment of this antigen using the Ki-67 antibody or other equivalent antibodies is commonly performed to measure cell proliferation in situ. |
| 2019 |
Ki67/MelanA |
Ki67/Melan A Double Stain or Dual Stain |
88344 |
The Ki-67 antigen is a proliferation marker and is expressed by cells within the cell cycle but not in resting cells. Studies have shown this antigen to be expressed throughout S phase, G2 phase and M phase of the cell cycle but absent in G0. It is a nuclear antigen and monoclonal antibodies have been developed that are suitable for use in paraffin embedded tissue sections. Assessment of this antigen using the Ki-67 antibody or other equivalent antibodies is commonly performed to measure cell proliferation in situ.5-10 Melan-A, product of MART-1 gene, is a differentiation antigen which is expressed in 100% of melanocytes, most melanomas, and 50-60 percent of melanoma cell lines. It was identified as one of the melanoma antigens recognized by autologous cytotoxic T cells, and as an antigenic target for tumor infiltrating lymphocytes. Melan-A expression has been shown to disappear with time and disease progression in a small percentage of subjects. It has been suggested that the loss of expression of these antigens is a defense mechanism the melanoma cell uses to escape immunosurveilance. This antibody also stains Melan-A in normal melanocytes and in retina. It does not stain normal or tumor tissues from nonmelanocyte lineages. |
| 2020 |
Lambda (P) |
LAMBDA LIGHT CHAINS |
88342 |
The human immunoglobulins basically consist of two identical heavy chains (Mr about 50 000) and two identical light chains (Mr about 20 000). The four chains are covalently linked together by disulphide bonds. The light chains are either kappa or lambda. The five immunoglobulins, IgA, IgD, IgE, IgG and IgM, differ regarding the heavy chains, and IgA and IgM also occur in polymeric forms. Individual B cells express either kappa or lambda light chains, but never both. In a polyclonal population the ratio of kappa to lambda bearing B cells is 2:1, and the occurrence of a mixture of kappa and lambda light chain-bearing cell types suggests polyclonality and a reactive or non-neoplastic proliferation of B cells. Diseases, such as multiple myeloma and B-cell lymphoma, are characterized by the proliferation of monoclonal neoplastic plasma cells producing only one type of light chain. Thus, the demonstration of a kappa or lambda light chain-restricted cell population is very useful in the histopathological diagnosis of these diseases. Primary AL (amyloid light-chain) amyloidosis is also a plasma cell disorder where the demonstration of monotypic kappa or lambda light chain in the amyloid deposits is diagnostically important and separates this disease from AA amyloidosis where immunoglobulin light chain deposits do not occur. In immunocytochemistry, the antibody labels plasma cells and related lymphoid cells containing kappa light chains, and it is a useful tool for the classification of patients with monoclonal gammopathies and amyloidosis. Additionally, the antibody may be used for distinguishing neoplastic monoclonal proliferation from reactive hyperplasia of B cells. Differential identification is aided by the results from a panel of antibodies. |
| 2021 |
Langerin (P) |
CD207 |
88342 |
Langerin is a highly selective marker for benign Langerhans cells and for the lesional cells of Langerhans cell histocytosis. Langerhans cells are normally present in many tissues, including lymph node and skin (tissues that could be used as positive controls). Langerin (CD207) is a type II Ca2+-dependent lectin associated with the formation of Birbeck granules in Langerhans cells. The staining pattern for Langerin is cytoplasmic. IHC evaluation for Langerin expression may have utility in substantiating a diagnosis of Langerhans cell histiocytosis and in distinguishing this disorder from other non-Langerhans cell histiocytic proliferations.Aod |
| 2022 |
LEF1 (EP310) |
Lymphoid Enhancer Binding Factor 1, TCF1ALPHA |
88342 |
Lymphoid enhancer-binding factor-1 (LEF1), also known as T cell factor protein 1 alpha (TCF-1α), is a member of the LEF/TCF family of transcription factors. LEF1 plays a key role in the WNT signaling pathway via direct interaction with β-catenin and subsequent induction of target gene expression such as cyclin D1 and c-myc. WNT signaling is a well known pathway in regulating cell proliferation and survival. LEF1 is normally expressed in T and pro-B cells but not mature B cells. Recent findings suggest that nuclear overexpression of LEF1 is highly associated with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL). Here, we developed a protocol of LEF-1 immunohistochemical stain and evaluated its usefulness in diagnosis of CLL/SLL and differentiation of this entity from follicular and mucosa-associated lymphoid tissue (MALT) lymphomas. |
| 2023 |
LH (C93) |
Luteinizing hormone |
88342 |
This antibody labels luteinizing hormone in normal and neoplastic tissue. LH labels gonadotropic cells of the pituitary. Dako LH, C93 is useful in the classification of pituitary adenomas and in the differential diagnosis of primary and metastatic tumors of the pituitary. |
| 2024 |
LMO2 (SP51) |
LIM domain only 2; LIM-only transcription factor-2; rhombotin-like 1 |
88342 |
LMO2 is expressed in normal germinal center B-cells and in a subset of lymphomas derived from those cells in addition to bone marrow hematopoietic precursors and endothelial cells. LMO2 protein expression also plays an important role in the diagnosis of diffuse large B-cell lymphomas, regardless of rituximab treatment. It is weakly expressed in mantle zone B-cells but not in mantle cell or marginal zone lymphomas. SF Younes et al. have demonstrated LMO2 expression in 70% of follicular lymphomas. |
| 2025 |
MAL (E-1) |
Myelin and Lymphocyte Protein |
88342 |
MAL (myelin and lymphocyte protein), also known as T lymphocyte maturation-associated protein, is a nonglycosylated hydrophobic integral membrane protein belonging to the MAL family of proteolipids. MAL is highly enriched in nervous system myelin and in rafts and apical membranes of epithelial cells. It is involved in forming, stabilizing and maintaining glycosphingolipidenriched membrane microdomains. MAL maintains the myelin sheath and, by controlling the sorting and trafficking of oligodendrocytes, it is involved in central nervous system paranode maintenance. MAL is a component of lipid rafts in myelinating cells. Association with glycosphingolipids may result in protein-lipid microdomain formation in myelin. MAL has been localized to the endoplasmic reticulum of T cells and in compact myelin of cells in the nervous system. MAL is primarily expressed by oligodendrocytes and Schwann cells in the intermediate and late stages of T cell differentiation. |
| 2026 |
MAMMAGLOBIN (31A5) |
Mammaglobin-1, Secretoglobin family 2A member 2, MGB1, UGB2. |
88342 |
Breast cancer is known for its morphologic diversity and diagnosis of metastatic breast carcinoma can be challenging. Mammaglobin is a breast-associated glycoprotein that belongs to the secretoglobin superfamily. It is expressed by normal mammary tissue and overexpressed in a subset of breast carcinomas. Studies have shown that mammaglobin is a useful marker in the diagnosis of primary and metastatic breast carcinoma. So far, the reported sensitivity of mammaglobin in identification of breast carcinoma has ranged from 48 to 76%. Although mammaglobin is relatively specific for breast carcinoma, some melanomas (about 6%) and ovarian carcinomas (about 3%) have been reported positive by immunohistochemistry (IHC). We developed a protocol for performing mammaglobin IHC and validated its usage in aiding in the diagnosis of breast carcinoma. |
| 2027 |
McPyV (CM2B4) |
Merkel Cell Polyomavirus |
88342 |
Merkel cell polyomavirus (MCPyV) infections are typically benign. However, in rare instances, these infections can lead to a neoplastic transformation of Merkel cell carcinoma through the expression of MCPyV large T-antigen (nuclear expression). Merkel cell carcinoma is a neuroendocrine malignancy that is frequently associated with MCPyV. Studies have shown that MCPyV can be detected by immunohistochemistry is approximately 58% of cases. Additionally, the presence of significant viral load in tumors is predictive of better prognosis. |
| 2028 |
MDM2 (IF2) |
mouse (or murine) double minute 2 |
88342 |
Well-differentiated liposarcoma / atypical lipomatous tumor (WDLS/ALT) are among the most common malignant soft tissue tumors presenting in older adults. These tumors typically arise in the deep soft tissue of the proximal lower extremities as slow growing masses or in the retroperitoneum with symptoms related to the presence of an abdominal mass. WDLS/ALT are often difficult to distinguish morphologically from benign lipomatous tumors, especially on needle biopsy specimens that lack evidence of hyperchromatic nuclei, the histologic feature most reliable for a diagnosis of WDLS/ALT, which may be widely scattered and not sampled in a small biopsy specimen. WDLS/ALT have been shown by cytogenetics to harbor ring and giant marker chromosomes consisting of amplicons of the 12q13-15 region, resulting in amplification of several genes, including most notably MDM2. MDM2 (murine double minute) gene is an oncogene whose expression plays an important role in controlling the cell cycle and therefore tumorigenesis by being responsible through a complex interaction for the degradation of the tumor suppressor protein p53. MDM2 expression has been shown by immunohistochemistry to be a useful adjunctive tool and reproducible way to distinguish WDLS/ALT from their histologic mimickers – benign lipomatous tumors. |
| 2029 |
MEF2B (EPR22192-78) |
Myocyte Enhancer Factor 2B, RSRFR2, Serum Response Factor-Like Protein 2, MADS Box Transcription Enhancer Factor 2 |
88342 |
Myocyte Enhancer Factor 2B (MEF2B) is a product of the MADS/MEF2 family of DNA binding proteins initially identified as important regulators of myocyte differentiation. MEF2B is highly expressed in germinal center B-cells and appears critical in germinal center formation. It is an activator of the BCL6 proto-oncogene in normal germinal centers. Mutations in MEF2B have been associated with lymphoma development. Expression patterns of MEF2B within lymphoproliferative disorders can be useful for diagnosis, particularly to help differentiate lymphomas of germinal center B-cell origin. |
| 2030 |
Melan A (A103) |
MART-1 |
88342 |
Melan-A, product of MART-1gene, is a differentiation antigen which is expressed in 100% of melanocytes, most melanomas, and 50-60 percent of melanoma cell lines. It was identified as one of the melanoma antigens recognized by autologous cytotoxic T cells, and as an antigenic target for tumor infiltrating lymphocytes. Melan-A expression has been shown to disappear with time and disease progression in a small percentage of subjects. It has been suggested that the loss of expression of these antigens is a defense mechanism the melanoma cell uses to escape immunosurveilance. This antibody also stains Melan-A in normal melanocytes and in retina. It does not stain normal or tumor tissues from nonmelanocyte lineages. |
| 2031 |
MiTF (C5+d5) |
Microphthalmia Transcription Factor |
88342 |
MiTFis a transcription factor implicated in pigmentation, bone development and in mast cells. Various forms of Mi exist ranging from 50-70 kD in size. This antibody targets the 52-56 kD range. This antibody has been useful in identifying malignant melanoma, and distinguishing mast cell lesions from lesions of myeloid derivation. A relatively rare class of tumors known as PEComas (tumors showing perivascular epithelioid cell differentiation) express MiTF in a high percentage of cases (~90%). |
| 2032 |
MLH-1 (M1) |
MutL homolog 1 (E. coli) |
88342 |
The anti-MLH1 antibody, clone M1, recognizes MLH1, one of several mismatch repair (MMR) proteins that are mutated in families with hereditary non-polyposis colorectal cancer (HNPCC). Carriers of these mutations have a high risk of developing colorectal, uterine, gastric, ovarian, skin, and other cancers due to accumulation of DNA replication errors in proliferating cells, called microsatellite instability (MSI). Microsatellites are short, repetitive DNA sequences that are prone to errors during DNA replication. Microsatellite instability (MSI) is characterized by alterations in the length of these sequences. It indicates a failure to repair certain errors during DNA replication and serves as a marker of a defect in at least one of the DNA mismatch repair (MMR) proteins. In normal cells, the MLH1 protein forms complexes (heterodimers) with PMS2 protein. When DNA mismatches occur, heterodimers of the other two MMR proteins, MSH2 and MSH6, bind to the mismatched DNA causing conformational changes. HNPCC represents 1-3% of all colorectal cancers with MLH1 loss occurring in the majority of them. Loss of MLH-1 expression is almost always accompanied by PMS-2 loss, however PMS-2 loss can sometimes be seen without loss of MLH-1. Assessment of DNA mismatch repair, either through MSI analysis or immunohistochemical-based evaluation of protein expression, may have predictive or prognostic relevance. |
| 2033 |
MOC-31 (MOC-31) |
Anti-Epithelial Specific Antigen |
88342 |
MOC-31 is a monoclonal antibody which recognizes an approximately 41-kilodalton, membrane-based glycoprotein (epithelial glycoprotein2, EGP-2) of unknown function. Immunohistochemical studies have shown that MOC-31 is expressed in a wide range of carcinomas and adenocarcinomas but not in lymphomas, melanomas, neuroblastomas or mesotheliomas. Clinically, MOC-31 stain has been demonstrated to be useful in differentiating adenocarcinoma from reactive mesothelial cells and mesotheliomas. |
| 2034 |
MSH-2 (G219-1129) |
MutS homolog 2 (E. coli) |
88342 |
MSH2 is a mismatch repair gene which is deficient in a high proportion of patients with microsatellite instability (MSI-H). This finding is associated with the autosomal dominant condition known as hereditary nonpolyposis colon cancer (HNPCC). The anti-MSH2 antibody is useful in screening patients and families for this condition. It has been shown that colon cancers that are microsatellite unstable have a better prognosis than their microsatellite stable counterparts. Anti-MSH2 is utilized in an IHC panel that includes anti-MLH1, anti-MSH6, and anti-PMS2. Loss of expression of MSH-2 is almost always accompanied by loss of MSH-6 expression, but loss of MSH-6 expression can sometimes be seen without accompanying loss of MSH-2. Assessment of DNA mismatch repair, either through MSI analysis or immunohistochemical-based evaluation of protein expression, may have predictive or prognostic relevance. |
| 2035 |
MSH-6 (SP93) |
mutS homolog6 |
88342 |
Colorectal cancer (CRC) is the third most common cancer and the fourth most prevalent cause of death in the world. The majority of CRCs show chromosomal instability, however approximately 15% of cancers develop through an alternative pathway characterized by defective function of the DNA mismatch repair (MMR) system. As a consequence of the MMR deficiency, tumors exhibit microsatellite instability (MSI) resulting from the inability of MMR proteins to repair DNA replication errors. CRCs with MMR defects are denoted as deficient MMR (dMMR) tumors. In contrast, CRCs with no MMR defects are denoted as proficient MMR (pMMR) tumors. The dMMR colorectal cancers are often poorly differentiated and frequently show proximal colon predominance, mucinous, medullary, or signet ring histologic features and increased numbers of tumor-infiltrating lymphocytes. In general, MMR deficiency may be caused either by germline mutations in one of the MMR genes with subsequent loss of the corresponding normal allele through genetic or epigenetic mechanisms, somatic mutations in the alleles, or by epigenetic inactivation of the MLH1 gene through methylation. The four most commonly mutated MMR genes are MLH1, PMS2, MSH2, and MSH6. In normal cells, the MLH1 protein forms a complex (heterodimer) with the PMS2 protein, while the MSH2 protein forms a complex with the MSH6 protein. When DNA mismatches occur, the MSH2/MSH6 heterodimer binds to the mismatched DNA, inducing a conformational change. The MLH1/PMS2 heterodimer binds the DNA-bound MSH2/MSH6 complex resulting in excision repair of the affected DNA. The MLH1, PMS2, MSH2, and MSH6 proteins are clinically important MMR proteins encoded by genes that may be mutated in families with Lynch syndrome. Carriers of these mutations have a high lifetime risk of developing colorectal and other cancers due to accumulation of DNA replication errors in proliferating cells. Lynch syndrome represents 16% of all CRCs. These tumors result from the inheritance of a germline autosomal dominant mutation in one of the four MMR genes, with MLH1 loss occurring in the majority of these Lynch syndrome associated CRCs. More than 300 different mutations in the MMR family of proteins have been identified in patients with Lynch syndrome. The Lynch syndrome-associated tumor phenotype is generally characterized by immunohistochemical loss of expression in MMR proteins, particularly MLH1, PMS2, MSH2, and MSH6. MMR IHC testing has been shown to be useful in the identification of the specific MMR gene in which either a germline or a somatic alteration is most likely to be found. Lynch syndrome was described in the 1960s and identified a link between the loss of MMR function and cancer. Loss of MMR proteins (MLH1, PMS2, MSH2 or MSH6) may lead to MSI and a higher lifetime risk of not only CRC, but also cancers of the stomach, brain, pancreas, skin, endometrium and ovaries. Patients with Lynch syndrome have a 50-80% lifetime risk for CRC. Lynch syndrome is unique from other hereditary cancer syndromes as direct testing on tumor tissue aids in the identification of patients at risk for Lynch syndrome and helps inform subsequent germline genetic testing. Families with Lynch syndrome benefit from advanced cancer screening protocols. Various guidelines, including those of the National Comprehensive Cancer Network (NCCN), recommend that all CRCs should be screened for potential Lynch syndrome to identify patients and families that will benefit from further genetic testing and counseling. Using a MMR IHC panel will aid in determining the MMR status of CRCs by classifying them as intact or loss for MMR protein expression. Detection of all four MMR proteins in the tumor indicates normal or intact MMR. Loss of MLH1 or MSH2 expression is almost invariably accompanied with the loss of its heterodimer partner, PMS2 or MSH6, respectively. However, loss of PMS2 or MSH6 does not lead to loss of MLH1 or MSH2. Loss of PMS2, MSH2, and/or MSH6 is consistent with probable Lynch Syndrome, and patients should be referred for additional testing and counseling consistent with clinical practice. |
| 2036 |
MUC-4 (8G-7) |
Mucin 4 |
88342 |
MUC4 (mucin 4) is a large membrane-anchored glycoprotein of the mucin family that is expressed by epithelial cells in various normal tissues including lung, bronchus, stomach, colon, and cervix. MUC4 is generally not detected in normal pancreas but is expressed in the vast majority of pancreatic neoplasms, such as pancreatic ductal adenocarcinoma. Additionally, expression in various carcinomas has been reported, including gastric adenocarcinoma, colon adenocarcinoma, and lung adenocarcinoma. |
| 2037 |
MUM-1 (MUM1p) |
IRF4 |
88342 |
MUM1 protein (multiple myeloma oncogene-1) is a 50 kDa protein encoded by the MUM1 gene that was originally identified because of its involvement in the rare t(6;14) (p25;q32) translocation observed in multiple myeloma (MM), causing juxtaposition of the MUM1 gene to the Ig heavy chain locus. MUM1-protein-deficient mice are unable to form germinal centers, lack plasma cells in the spleen and lamina propria, and exhibit a profound reduction of serum immunoglobulin levels and an inability to mount detectable antibody responses or to generate T-lymphocyte cytotoxic or antitumor responses. Expression of MUM1 protein is independent from the t(6;14) (p25;q32) translocation and has been detected in multiple myelomas, lymphoplasmacytic lymphomas (LPL), diffuse large B-cell lymphomas (DLBCL), and activated T cells. MUM1 protein is not specific for plasmacytic differentiation, but it may be added to the panel of phenotypic markers available for characterization of B-cell lymphoma histogenesis, in addition to being a useful marker in the subclassification of lymphoid malignancies, e.g. in B-CLL. MUM1 protein expression is restricted to cells in the lymphocytic and melanocytic lineages. |
| 2038 |
Muramidase (P) |
Lysozyme |
88342 |
Muramidase (Lysozyme) has been shown to have cytoplasmic expression in hematopoietic cells and non-hematopoietic cells, like renal proximal convoluted tubules. Lysozyme may be used as a non-specific marker of tissue macrophages (such as alveolar macrophages and liver Kupffer cells), histiocytes, monocytes, myeloid cells, and their proliferations and neoplasms. Anti-lysozyme may aid in the identification of histiocytic lesions and neoplasms, acute myelomonocytic leukemia, acute monocytic leukemia and Langerhans cell histiocytosis. |
| 2039 |
Myeloperoxidase (EP151) |
MPO |
88342 |
Anti-myeloperoxidase detects granulocytes and monocytes in blood and precursors of granulocytes in the bone marrow. This antibody can detect myeloid cell populations of the bone marrow as well as in other sites. This antibody is indicated as an aid in the identification of lymphoid and myeloid disorders. |
| 2040 |
MyoD1 (EP212) |
Myogenic Differentiation 1Ce |
88342 |
The MyoD1 protein is a 45 kD nuclear phosphoprotein which induces myogenesis through transcriptional activation of muscle-specific genes. Nuclear expression of MyoD1 is restricted to skeletal muscle tissue and has been demonstrated to be a sensitive marker of myogenic differentiation. Rhabdomyosarcoma (RMS) is a malignant tumor comprised of neoplastic cells with evidence of skeletal muscle differentiation. MyoD1 immunostaining has been found in the tumor cell nuclei of the majority of RMS. Therefore, immunohistochemical evaluation for MyoD1 expression may have utility in supporting a diagnosis of rhabdomyosarcomas and in distinguishing this tumor from other tumor types. |
| 2041 |
Myogenin (F5D) |
BHLHc3, Myogenic Factor 4 |
88342 |
Anti-Myogenin labels the nuclei of myoblasts in developing muscle tissue, and is expressed in tumor cell nuclei of rhabdomyosarcoma and some leiomyosarcomas. Positive nuclear staining may occur in Wilm’s tumor. |
| 2042 |
Napsin A (EP205) |
Napsin A aspartic peptid |
88342 |
Napsin A is an aspartic proteinase and plays a role in pneumocyte surfactant processing. It is expressed in normal adult lung tissue, specifically labeling type II pneumocytes and epithelial cells in kidney tissues. Recent studies have demonstrated that Napsin A was expressed in more than 80% of lung adenocarcinoma cases. Additionally, a small number of lung adenocarcinoma cases that were negative by the commonly used marker, thyroid transcription factor 1 (TTF-1), showed positive Napsin A immunohistochemistry (IHC) staining. These findings suggest that Napsin A can be a useful adjunct to TTF-1 for differentiation of non-small cell lung cancer. We developed a protocol for performing Napsin A IHC and validated its usage in aiding the differential diagnosis of pulmonary adenocarcinoma from squamous cell carcinoma. |
| 2043 |
Neu-N (A60) |
Neuronal nuclei |
88342 |
NeuN antibody (Neuronal Nuclei; clone A60) specifically recognizes the DNA-binding, neuron-specific protein NeuN, which is present in most CNS and PNS neuronal cell types of all vertebrates tested. NeuN protein distributions are apparently restricted to neuronal nuclei, perikarya and some proximal neuronal processes in both fetal and adult brain although some neurons fail to be recognized by NeuN at all ages: INL retinal cells, Cajal-Retzius cells, Purkinje cells, inferior olivary and dentate nucleus neurons, and sympathetic ganglion cells are examples. Immunohistochemically detectable NeuN protein first appears at developmental timepoints that correspond with the withdrawal of the neuron from the cell cycle and/or with the initiation of terminal differentiation of the neuron. Focal cortical dysplasias (FCD) are localized regions of malformed cerebral cortex which have been closely associated with drug-resistant epilepsy. FCDs encompass a spectrum of different lesions that share histologic common denominators such as abnormal cortical architecture. The International League Against Epilepsy (ILAE) classification system, published in 2011, has replaced the previous “Palmini classification system” and become a new international standard. The ILAE classification system requires labeling neuronal cell bodies using neuronal nuclei antigen (NeuN) immunohistochemistry (IHC). Additionally, ILAE classification of hippocampal sclerosis (2013), another epileptogenic lesion, also specified that NeuN was the most valuable immunostaining for the assessment of neuronal cell loss in surgical specimens from drug-resistant temporal lobe epilepsy. We developed a protocol for performing NeuN IHC staining and validated its usage in aiding histopathological diagnosis of FCD. Since NeuN is considered to be a marker of neuronal differentiation, we also evaluated the potential use of NeuN in differential diagnosis of brain tumors such as central neurocytomas and gangliogliomas. |
| 2044 |
Neurofilament (2F11) |
NF |
88342 |
Neurofilaments (NFs) belong to the family of intermediate filaments (IFs) and are structural elements of the neuronal cytoskeleton in an interconnection with actin microfilaments, microtubules and other IFs. NFs are composed of three different subunits that are different, but related proteins: NF-L (70 kDa), NF-M (150-160 kDa) and NF-H (200 kDa). The antigenic determinants of each of the subunits may be unique or shared and each NF subunit is a separate gene product. During embryonic neurogenesis, the NF-L and NF-M subunits are coexpressed, whereas the activation of the NF-H subunit is delayed to the postnatal period. NF-M and NF-H subunits are unable to self-assemble and, typically, form co-polymers with NF-L. |
| 2045 |
Neurofilament 2F11 and SMI-32 Cocktail (2f11&SMI32) |
NF COCKTAIL |
88342 |
The diagnosis of primary demyelination is dependent upon the detection of myelin loss (identified by Luxol Fast Blue stain) with relative preservation of axons, identified by neurofilament immunostain. For this reason, detection of all axons present in a biopsy specimen is essential for correct diagnosis. The anti-human neurofilament protein, clone 2F11, stains low molecular weight neurofilament (NF-L). Meanwhile, the clone SMI-32 recognizes non-phosphorylated high molecular weight neurofilament (NF-H). The cocktail staining using both clone 2F11 and SMI-32 should provide better visibility of axons than the 2F11 stain alone, thus improving accuracy of the diagnosis. |
| 2046 |
NK1/C3 (NK1/C3) |
CD63 |
88342 |
CD63 is a 53kDa lysosomal membrane protein in the family of tetraspan moieties, and characterized as an activation dependent platelet surface antigen. Anti-CD63 reactivity is seen in the cytoplasm of many cell types including lymphoid, myeloid, endothelial cells, and the majority of malignant melanomas. Anti-CD63 is a useful immunohistochemical marker for the identification of malignant melanoma. |
| 2047 |
NKX3.1 (P) |
NK3 Homeobox 1, NKX3, BAPX2, NKX3A, NKX3.1, Bax, bagpipe, NKX3-1 |
88342 |
NKX-3.1 is a protein found in humans and is encoded by the NKX3-1 gene located on chromosome 8. The homeodomain containing transcription factor NKX3A is a putative prostate tumor suppressor that is expressed in a largely prostate-specific and androgen-regulated manner. NKX3.1 protein has been found to be positive in the vast majority of primary prostatic adenocarcinomas. NKX3.1 stains nuclei in both normal and prostate cancer; thus providing a robust stain that is easy-to-interpret, similar to other transcription factors such as TTF-1 or CDX2. In the appropriate clinical setting, the addition of IHC staining for NKX3.1, along with other prostate-restricted markers, may prove to be a valuable adjunct to definitively determine prostatic origin in poorly differentiated metastatic carcinomas. NKX3.1 used in combination with ERG monoclonal antibody [9FY], may represent one of the most sensitive and specific markers for identifying tumors of prostatic origin. |
| 2048 |
NPM-1 (P) |
mutated nucleophosmin 1, mutated B23 |
88342 |
The presence of NPM1 mutations are frequently identified within acute myeloid leukemia. The presence of an NPM1 in the appropriate setting can be used to define a category of AML (AML with mutated NPM1) within the 2016 WHO monograph and tend to be seen in the setting of normal karyotype. They are generally associated with a more favorable outcome, particularly in the absence of an associated FLT3 mutation or internal tandem repeat. The blasts often show a monocytic phenotype with absence of CD34 expression, and multilineage dysplasia can be observed in a significant subset raising potential consideration of AML with myelodysplasia-related changes. In the setting of NPM1 mutation, however, the dysplasia does not confer a worse prognosis. This mutation is also seen with relative frequency in the setting of myeloid sarcoma. The potential to detect NPM1 mutation within bone marrow or involved tissue sites is of utility given that the blast phenotype is often not specific, the presence of the mutation is of potential prognostic significance and molecular studies can take days to weeks to complete. Somatic mutations of this gene alter subcellular localization of the product nucleophosmin into the cytoplasm, improving potential detection of the presence of abnormal protein by IHC. Such methods can also be used to follow residual disease involvement in the bone marrow as phenotype and differentiation status may be altered by therapy. NPM1 mutations can also be seen in a subset of non-AML myeloid neoplasms, where they appear to confer a worse prognosis. |
| 2049 |
NRAS (RBT-NRAS) |
NRAS Proto-Oncogene, GTPase with Q61R mutation |
88342 |
NRAS oncogene is a member of the Ras gene family which is involved in normal control of cell growth. Mutations in NRAS have been seen in melanomas, acute myeloid leukemia and thyroid cancers. Specifically, the NRAS (Q61R) mutation has been associated with a subset of melanomas, acute myeloid leukemias, and thyroid cancers. Therefore, identification of NRAS (Q61R) mutation by immunohistochemistry is a time and tissue efficient screen for the diagnosis of a subset of melanomas, acute myeloid leukemias and thyroid cancers. |
| 2050 |
NUT (C52B1) |
NUTM1, NUT midline carcinoma family member 1; Nuclear protein in testis |
88342 |
Nuclear protein in testis (NUT), which is normally expressed only in germ cells of the testis and ovary, regulates TERT expression by modulating SP1 binding to TERT promoter binding sites. NUT midline carcinoma (NMC) is a rare, clinically aggressive carcinoma that is characterized by rearrangements of the NUTM1 gene, most often in the form of a t(15;19) NUTM1-BRD4 fusion gene. Other NUTM1 rearrangements also have been described. Immunohistochemistry using a sensitive NUT antibody such as C52B1 facilitates the diagnosis of NMC. |
| 2051 |
OCT 2 (MRQ2) |
Octamer Transcription Factor 2 |
88342 |
Oct-2 is a transcription factor of the POU homeo-domain family that binds to the Ig gene octamer sites, regulating B-cell-specific genes. These are involved in proliferation and differentiation and, despite the scarce evidence for Oct-2 expression in T cells, it has been shown that this factor participates in transcriptional regulation during T-cell activation. Oct-2 activity is dependent on phosphorylation and alternative splicing. Various lymphomas are also positive for this marker including B-chronic lymphocytic leukemia, mantle cell lymphoma, follicular lymphoma, marginal zone lymphoma, plasmacytoma, Burkitt lymphoma, diffuse large cell lymphoma, diffuse large B-cell lymphoma, T-cell rich B-cell lymphoma, nodular lymphocyte predominant Hodgkin lymphoma, and classic Hodgkin lymphoma. |
| 2052 |
OCT 3/4 (C-10) |
POU5F1 (POU domain, class 5, transcription factor 1 |
88342 |
The recently described marker, OCT3/4, a nuclear transcription factor and marker of pluripotency, has been found in both normal immature and malignant germ cells, known as carcinoma in situ/intratubular germ cell neoplasia unclassified (CIS/ITGCNU). ITGCNU is the common precursor of all type II testicular germ cell tumors (TGCTs) which can be diagnosed using a surgical biopsy. ITGCNU derives from undifferentiated germ cells, gonocytes, which persist in the newborn testis and escape the normal differentiation process. Germ cell tumors (GCT) comprise a heterogeneous group of benign and malignant tumors. Based on their different biological characteristics and their origin, five types of GCT are classified. Among these, malignant seminomatous and non-seminomatous GCT in males and females are designated as type II GCT. They occur most frequently as malignant testicular GCTs. New diagnostic markers for neoplastic germ cells, including OCT3/4, are specifically detected in ITGCNU, seminomas and embryonal carcinomas and are helpful in the differentiation of GCT from other malignant tumors. |
| 2053 |
Olig2 (211F1.1) |
Oligodendrocyte transcription factor / Oligodendrocyte lineage transcription factor 2 |
88342 |
Olig2, a basic helix-loop-helix (bHLH) transcription factor, is involved in oligodendroglial specification. Olig2 expression was restricted to glial tumors and nontumoral oligodendrocytes. It was higher in oligodendrogliomas when compared to astrocytomas. In addition, there is no olig2 expression in the non-glial tumors including neuroepithelial tumors, medulloblastomas, and non neuroepithelial tumors. However, a diagnosis of oligodendroglioma may be challenging with currently available morphological classification. Olig2 immunohistochemistry has been reported as a useful marker to assist diagnosis of patients with oligodendrogliomas. |
| 2054 |
P120 catenin (98) |
CTNND1, Catenin Delta 1, P120 |
88342 |
p120 catenin is a tyrosine kinase that binds to E-cadherin within the cell membrane. Absence of E-cadherin at the cell membrane transports p120 catenin into the cell cytoplasm. Cytoplasmic expression of p120 catenin is useful in the distinction between lobular breast neoplasia (cytoplasmic staining pattern) versus ductal breast neoplasia (membranous staining pattern). |
| 2055 |
P16 (E6H4) |
CDKN2A, Cycln Dependent Kinase Inhibitor 2A, CDK4, Inhibitor P16-INK4 |
88342 |
As a cyclin-dependent kinase inhibitor, p16INK4a (p16) plays a key role in cell cycle regulation and cellular differentiation. The p16 protein controls the retinoblastoma protein (pRB)-mediated G1-S phase transition and triggers cell cycle arrest in the course of the cellular differentiation process. In normal, terminally differentiated cells, p16 is expressed at low levels typically not detectable by immunohistochemistry (IHC). Research studies have identified strong overexpression of p16 in pre-cancerous and cancerous tissues to be closely linked to the expression of human papillomavirus (HPV) E7 oncoprotein. IHC detection of p16 overexpression may aid in the interpretation of cervical histology specimens. The p16 protein has been reported to be over-expressed in squamous neoplastic epithelial cells of the cervix uteri, whereas it has been found to be mostly absent in normal epithelium and non-neoplastic lesions. Numerous studies have investigated the correlation between p16 overexpression and the presence of cervical intraepithelial neoplasia (CIN). Overexpression of p16 has been observed in virtually all CIN3 lesions, the vast majority of CIN2 lesions, and typically within 40% to 60% of squamous cervical lesions classified as CIN1 in Hematoxylin and Eosin (H&E) stained tissue sections. |
| 2056 |
P40 (BC28) |
ΔNp63 |
88342 |
The mouse monoclonal antibody p40 [clone BC28] recognizes an epitope unique to the p40 protein and may have applications in cases where p63 has traditionally been used. To date, p63 [clone 4A4] has been a frequently used marker for lung squamous cell carcinoma (SCC), as well as for bladder, breast, prostate, and head and neck cancers. p63 [4A4] recognizes both the p63 and p40 proteins. As a result, p63 [4A4] has proven to be a sensitive marker for lung SCC; however, it suffers from specificity limitations due to reactivity in a subset of lung adenocarcinomas (ADC). In contrast, p40 is selectively expressed in lung SCC, offering an opportunity for improved specificity. p40 (M) [BC28] recognizes an epitope unique to p40, which may result in diminished reactivity in lung ADC and increased specificity. |
| 2057 |
P53 (DO-7) |
Tumor protein 53, TP53 |
88360 |
p53 is a nuclear phosphoprotein with a molecular mass of 53 kDa. Wild-type p53 protein is present in a wide variety of normal cells, but the protein has a very short half-life and thus is present in only minute amounts, generally below the detection level of immunocytochemical methods. Somatic mutation of the p53 gene is a very frequent event in the development of human neoplasia, and because mutant p53 proteins often are much more stable than wild-type p53 protein, the mutant p53 protein accumulates to a high level. As examples, p53 protein accumulation was observed in 76% of 212 human malignant lesions, including breast, colon and stomach carcinomas, melanoma, embryonal carcinoma of the testis, transitional carcinoma of the urinary bladder, uterine carcinoma and soft tissue sarcomas. Wild-type p53 protein functions as a transcription factor, i.e. as a modulator which can turn crucial genes either on or off. It also inhibits DNA replication and is a check-point control molecule for progression of the cell cycle. Furthermore, p53 protein is involved in the regulation of apoptosis. In transfection assays, wild-type p53 behaves as a tumor suppressor, while mutant p53 behaves as a dominant transforming oncogene. |
| 2058 |
P57 (AB6) |
CDKN1C |
88342 |
P57 protein is encoded by the CDKN1C gene, which is strongly paternally imprinted and expressed exclusively from the maternal allele. Complete hydatidiform mole (CHM) contains only paternal genes & has been proven to display reduced or absent P57 protein compared to partial hydatidiform mole (PHM) which contains both maternal & paternal genomes. IHC stain of P57 may be useful in the differential diagnosis of CHM and PHM. |
| 2059 |
P63 (A4A) |
KET, p53, p40, p73L |
88342 |
The human p63 protein is a member of the p53 family of transcription factors, and has six major isoforms. The p63 protein is highly expressed in the basal or progenitor cells of a variety of epithelial tissues, including those of the prostate, breast, esophagus, bladder, and epidermis and is important in the development of each of these tissues. In the prostate, p63 can be detected in the basal cells of almost all normal and benign glands, but is not present in the neuroendocrine or luminal, secretory cells. As basal cells are generally absent from invasive prostate carcinoma, the identification of p63 in normal prostatic gland aids in the identification of prostate carcinoma. In high grade prostate intraepithelial neoplasia (PIN), considered a precancerous lesion, dysplastic cells do not express p63, but a residual rim of p63-positive basal cells can be identified. Similarly, detection of p63 in normal breast myoepithelial cells may be useful in identification of breast neoplasms. In lung, p63 positivity of 77.8-100% has been reported among squamous cell carcinomas, while the majority of adenocarcinomas (88.7-100%) are negative for this marker. Thus, p63 as part of a panel of biomarkers may aid in the differentiation of lung squamous cell carcinoma and lung adenocarcinoma. |
| 2060 |
p63-ERG |
p63: KET, p51, p40, and p73L; ERG: ETS Transcription Factor ERG |
88344 |
The TMPRSS2-ERG gene fusion has been found to be highly specific for prostate cancer and presented in approximately 50% of prostate cancer cases. TMRRSS2-ERG gene fusions result in a truncated ERG protein product which can be detected by immunohistochemistry (IHC) using a rabbit anti-ERG monoclonal antibody. A double stain combining anti-ERG and anti-p63, a marker for basal cells of normal glands, will be able to distinguish tumor glands from normal glands in a subset of prostate cancers. Therefore, the p63/ERG double stain may have utility in substantiating a diagnosis of prostate cancer especially in needle biopsies where there is limited prostate cancer. |
| 2061 |
Pan-TRK (EPR17341) |
Tropomyosin receptor kinase proteins A, B, and C |
88342 |
Tropomyosin, or tyrosine, receptor kinase (Trk) family members play a role within the nervous system by binding neurotrophins to affect both neuronal differentiation and survival. The neurotrophic receptor kinase 1 (NTRK1), NTRK2, and NTRK3 genes encode proteins TrkA, B, and C respectively. In some instances, an NTRK gene fuses to an unrelated gene, causing Trk signaling to occur without control, which can lead to cancer. NTRK fusions are rare in most cancers, occurring in around 0.5–1% of common cancers, but are seen at higher frequencies (> 90%) in rare cancer types like secretory carcinoma and congenital fibrosarcoma. Pan-Trk immunohistochemistry can help determine whether translation occurs for novel NTRK rearrangements. Therefore, pan-Trk immunohistochemistry is a time and tissue efficient screen for NTRK fusions. |
| 2062 |
Parvovirus (R92F6) |
Erythrovirus B19, B19V |
88342 |
Parvovirus B19 manifestations of infection vary with the immunologic and hematologic status of the host. In the immunocompromised host persistent parvovirus B19 infection is manifested as pure red cell aplasia and chronic anemia. Likewise, the immature immune response of the fetus may render it susceptible to infection, leading to fetal death in utero, hydrops fetalis, or development of congenital anemia. The virus is also associated with erythema infectiosum (Fifth disease) in children and acute arthritis in adults. |
| 2063 |
PAX2 (EP235) |
Paired box gene 2 |
88342 |
PAX2 is a transcription factor that, during embryonic development, codes for a protein that is involved in the formation of the eye, ear, central nervous system, kidney, and genital tract. After birth, the PAX2 protein is thought to protect against cell death during periods of cellular stress. The PAX2 gene is overexpressed in certain cancers of the kidney, prostate, breast, and ovary. |
| 2064 |
PAX5 (SP34) |
B-cell specific activator protein (BSAP) |
88342 |
PAX5, also known as B-cell specific activator protein (BSAP), is a member of the paired box (PAX) family of transcription factors. Within lymphocytes, PAX5 is expressed in B-cell precursors and mature B-cells, but is lost as B-cells mature into plasma cells. PAX5 is also expressed in the neoplastic cells of >90% of classical Hodgkin lymphoma. |
| 2065 |
PAX8 (SP348) |
Paired Box 8 |
88342 |
PAX8 is a member of the paired box (PAX) family of cell lineage restricted transcription factors that are expressed in specific primordial tissues in the embryonic stages and in differentiated adult tissues. These lineage restricted transcription factors play a key role in the development of specific tissues and organs and are also useful in identifying the probable tissue origin of a tumor. Similar to PAX2, PAX8 is a nephric lineage marker and often co-expressed with PAX2. PAX8 immunoreactivity has been detected in renal tubular cells and in tissues of Müllerian origin including epithelial cells of the fallopian tube and endometrium, and tissues of Wolffian duct origin including vas deferens, and seminal vesicles. PAX8 expression has also been reported in neoplasms with nephric origin including renal cell carcinoma, nephrogenic adenoma and clear cell adenocarcinoma of the lower urinary tract. In addition, PAX8 is also known as a crucial transcription factor for organogenesis of the thyroid gland and Müllerian system. PAX8 may also be a useful marker in the diagnosis of ovarian or thyroid tumors. |
| 2066 |
PD1 (NAT105) |
Programmed Cell Death 1; CD279; Ly101 |
88342 |
Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) represents approximately 5% of all cases of Hodgkin lymphoma and is considered to be a distinct entity. The histologic findings often overlap with T-cell/histiocyte rich B-cell lymphoma (T/HRBCL), making diagnosis difficult. The presence of T-cell rosettes surrounding neoplastic cells is distinctive of NLPHL and is a helpful finding for distinguishing NLPHL from T/HRBCL. PD-1(NAT-105) is a T-cell marker that highlights T-cell rosettes in many cases of NLPHL while also marking germinal center T-cells. |
| 2067 |
PD-L1 (22C3) |
Programmed Death – Ligand 1 |
88360 |
Binding of the PD-1 ligands, PD-L1 and PD-L2, to the PD-1 receptor found on T cells, inhibits T cell proliferation and cytokine production. PD-L1 expression in tumor cells can be used as a prognostic indicator that anti-PD-1 immunotherapy may prolong life expectancy in patients with malignancies such as melanoma, lung, and bladder cancer. At the time of this writing (March 2017), PD-L1 (22C3) expression in advanced non-small cell lung cancer (NSCLC) is the companion diagnostic test for treatment with Merck Keytruda (pembrolizumab). It is prescribed for patients whose disease has progressed even after platinum-based chemotherapy, and as first-line treatment of patients with metastatic NSCLC. |
| 2068 |
PERFORIN (5B10) |
PRF1 |
88342 |
Perforin plays a key role in secretory granule-dependent cell death, and in defense against virus-infected or neoplastic cells. Plays an important role in killing other cells that are recognized as non-self by the immune system, e.g. in transplant rejection or some forms of autoimmune disease. Can insert into the membrane of target cells in its calcium-bound form, oligomerize and form large pores. Promotes cytolysis and apoptosis of target cells by facilitating the uptake of cytotoxic granzymes. |
| 2069 |
PIN3 (P504S+P63+34BE12) |
Prostatic intraepithelial neoplasia |
88344 |
This two-color, three-antibody stain includes 34β12 and p63 with a brown chromogen and p504s in a red chromogen. In the prostate, 34βE12 and p63 stain normal basal cells, while p504s (AMACR) is generally negative or only very faintly positive in normal glands. In invasive adenocarcinoma, there is loss of normal basal cells. In addition, 80% or more of invasive adenocarcinomas show luminal cytoplasmic expression of p504s (AMACR). |
| 2070 |
Pit-1 (D-7) |
POU1F1, POU Class 1 Homeobox 1 |
88342 |
Pit-1 determines the differentiation of growth hormone (somatotroph, lactotroph, and thyrotroph) cells within the pituitary gland. The nuclear expression of Pit-1 is retained in the pituitary tumor cells that are differentiated towards their respective pituitary cell lineage and therefore is useful in the classification of pituitary neuroendocrine tumors. |
| 2071 |
PLAG1 (3B7) |
PLAG1 Zinc Finger, ZNF912, Pleomorphic Adenoma Gene |
88342 |
PLAG1 gene plays an important role in the regulation of cell growth and differentiation. It belongs to the PLAG family of transcription factors and is expressed in a variety of tissues, including the salivary glands, pituitary gland, and adrenal gland. PLAG1 is frequently overexpressed in pleomorphic adenomas. Its overexpression is thought to contribute to the development of these tumors by promoting cell proliferation and inhibiting apoptosis. PLAG1 is also involved in the development of adult lipoblastoma, a rare benign tumor that arises from embryonic white fat cells. The detection of PLAG1 overexpression by IHC is a useful diagnostic tool for pleomorphic adenomas and adult lipoblastomas. |
| 2072 |
PLAP (8A9) |
Placental alkaline phosphatase |
88342 |
Placental alkaline phosphatase (PLAP) is normally produced by primordial germ cells and placental syncytiotrophoblasts, and the detection of its expression has been useful in identifying germ cell tumors. Anti-PLAP antibody immunoreacts with germ cell tumors and can discriminate between these and other neoplasms. Somatic neoplasms e.g. breast, gastrointestinal, prostatic and urinary cancers may also immunoreact with antibodies to PLAP. Anti-PLAP positivity in conjunction with keratin negativity favors seminoma over carcinoma. Germ cell tumors are usually keratin positive, but they regularly fail to stain with anti-EMA, whereas most carcinomas stain with anti-EMA. Anti-PLAP has been useful in the diagnosis of gestational trophoblastic disease. Complete hydatidiform mole shows strong expression of hCG and weak expression of PLAP. Weak hCG and strong PLAP expression is found in partial hydatidiform mole. Choriocarcinoma presents strong expression of hCG and weak expression of PLAP. In addition to its role as a germ cell marker, PLAP may also be used as a myogenic marker in identifying soft tissue tumors. Clone 8A9 detected PLAP and PLAP-like enzyme in the membrane of syncytiotrophoblasts of 11 placenta, 5/5 seminomas, 0/1 ovarian teratoma and 0/1 yolk sac tumor. No staining was seen in a variety of other tumors (n=37), except for occasional staining of striated and/or smooth muscle. |
| 2073 |
PMS2 (EP51) |
PMS1 Homolog 2 |
88342 |
Colorectal cancer (CRC) is the third most common cancer and the fourth most prevalent cause of death in the world. The majority of CRCs show chromosomal instability, however approximately 15% of cancers develop through an alternative pathway characterized by defective function of the DNA mismatch repair (MMR) system. As a consequence of the MMR deficiency, tumors exhibit microsatellite instability (MSI) resulting from the inability of MMR proteins to repair DNA replication errors. CRCs with MMR defects are denoted as deficient MMR (dMMR) tumors. In contrast, CRCs with no MMR defects are denoted as proficient MMR (pMMR) tumors. The dMMR colorectal cancers are often poorly differentiated and frequently show proximal colon predominance, mucinous, medullary, or signet ring histologic features and increased numbers of tumor-infiltrating lymphocytes. In general, MMR deficiency may be caused either by germline mutations in one of the MMR genes with subsequent loss of the corresponding normal allele through genetic or epigenetic mechanisms, somatic mutations in the alleles, or by epigenetic inactivation of the MLH1 gene through methylation. The four most commonly mutated MMR genes are MLH1, PMS2, MSH2, and MSH6. In normal cells, the MLH1 protein forms a complex (heterodimer) with the PMS2 protein, while the MSH2 protein forms a complex with the MSH6 protein. When DNA mismatches occur, the MSH2/MSH6 heterodimer binds to the mismatched DNA, inducing a conformational change. The MLH1/PMS2 heterodimer binds the DNA-bound MSH2/MSH6 complex resulting in excision repair of the affected DNA. The MLH1, PMS2, MSH2, and MSH6 proteins are clinically important MMR proteins encoded by genes that may be mutated in families with Lynch syndrome. Carriers of these mutations have a high lifetime risk of developing colorectal and other cancers due to accumulation of DNA replication errors in proliferating cells. Lynch syndrome represents 16% of all CRCs. These tumors result from the inheritance of a germline autosomal dominant mutation in one of the four MMR genes, with MLH1 loss occurring in the majority of these Lynch syndrome associated CRCs. More than 300 different mutations in the MMR family of proteins have been identified in patients with Lynch syndrome. The Lynch syndrome-associated tumor phenotype is generally characterized by immunohistochemical loss of expression in MMR proteins, particularly MLH1, PMS2, MSH2, and MSH6. MMR IHC testing has been shown to be useful in the identification of the specific MMR gene in which either a germline or a somatic alteration is most likely to be found. Lynch syndrome was described in the 1960s and identified a link between the loss of MMR function and cancer. Loss of MMR proteins (MLH1, PMS2, MSH2 or MSH6) may lead to MSI and a higher lifetime risk of not only CRC, but also cancers of the stomach, brain, pancreas, skin, endometrium and ovaries. Patients with Lynch syndrome have a 50-80% lifetime risk for CRC. Lynch syndrome is unique from other hereditary cancer syndromes as direct testing on tumor tissue aids in the identification of patients at risk for Lynch syndrome and helps inform subsequent germline genetic testing. Families with Lynch syndrome benefit from advanced cancer screening protocols. Various guidelines, including those of the National Comprehensive Cancer Network (NCCN), recommend that all CRCs should be screened for potential Lynch syndrome to identify patients and families that will benefit from further genetic testing and counseling. Using a MMR IHC panel will aid in determining the MMR status of CRCs by classifying them as intact or loss for MMR protein expression. Detection of all four MMR proteins in the tumor indicates normal or intact MMR. Loss of MLH1 or MSH2 expression is almost invariably accompanied with the loss of its heterodimer partner, PMS2 or MSH6, respectively. However, loss of PMS2 or MSH6 does not lead to loss of MLH1 or MSH2. Loss of PMS2, MSH2, and/or MSH6 is consistent with probable Lynch Syndrome, and patients should be referred for additional testing and counseling consistent with clinical practice. |
| 2074 |
Pneumocystis (3F6) |
P. jiroveci, P. carinii |
88342 |
Pneumocystis jiroveci, formerly known as Pneumocystis carinii, causes the disease Pneumocystis carinii pneumonia (PCP) which is one of the leading causes of illness and death in persons with impaired immunity caused by HIV, organ transplantation, or chemotherapy for malignant diseases. |
| 2075 |
PRAME (EPR20330) |
PReferentially expressed Antigen in MElanoma |
88360 |
PRAME (preferentially expressed antigen in melanoma) is an antigen that is preferentially expressed in human melanomas and that is recognized by cytolytic T lymphocytes. It is not expressed in normal tissues, except testis. The encoded protein acts as a repressor of retinoic acid receptor, and likely confers a growth advantage to cancer cells via this function. PRAME expression by immunohistochemistry has been reported in the majority of cases malignant melanoma and melanoma in situ, while PRAME expression is reported to be absent or only rarely identified in nevi. |
| 2076 |
Progesterone Receptor (1E2) |
PR |
88360 |
Determination of ER status for all primary breast carcinomas was recommended by the National Institutes of Health (NIH) in 1979, to better determine appropriate therapy. In 1985, both the NIH and the American Cancer Society independently published reports in support of determining hormone receptor status as an aid in the management of breast cancer. In 1996, the American Society of Clinical Oncology, based upon the findings of their Tumor Marker Panel, recommended the determination of ER and PR status on all primary lesions and on metastases if the results would influence treatment planning. They also recommended using the ER and PR results for identification of patients most likely to benefit from endocrine adjuvant therapy and therapy for recurrent or metastatic disease. The Tumor Marker Panel also noted that ER and PR status may play a role in prognosis, but cautioned that they should be evaluated in conjunction with other clinical criteria, as ER and PR status alone were relatively weak predictors of long term relapse and breast cancer-related mortality. |
| 2077 |
PROLACTIN (EP193) |
Luteotropin |
88342 |
Prolactin (PRL) is a single-chain polypeptide of 226 amino acids and plays a role in multiple processes including cell growth, reproduction, and immune function. Anti-Prolactin reacts with prolactin-producing cells and is a useful marker in classification of pituitary tumors and the study of pituitary disease. |
| 2078 |
PSA (EP109) |
Prostate Specific Antigen, Kallikrein-3 |
88342 |
PSA is a chymotrypsin-like serine protease (kallikrein family) produced by the prostate epithelium. Studies have shown that PSA is used to confirm prostatic acinar cell origin in primary and metastatic carcinomas and to rule out non-prostatic carcinoma mimics. |
| 2079 |
PSAP (PASE/4LJ) |
Prostate-specific acid phosphatase |
88342 |
Anti-PSAP reacts with prostatic acid phosphatase in the glandular epithelium of normal and hyperplastic prostate, carcinoma of the prostate, and metastatic cells of prostatic carcinoma. This marker may be helpful in pinpointing the site of origin in cases of metastatic carcinoma of the prostate, and is considered a more sensitive marker than PSA. However, it also offers less specificity. Nevertheless, PSAP complements PSA in the right clinical context. |
| 2080 |
PSMA (3E6) |
Prostate specific membrane antigen, GCP2 |
88342 |
Prostate specific membrane antigen (PSMA) is a 750 amino acid type II membrane glycoprotein with folate hydrolase and neuropeptidase activity. PSMA is expressed in normal and malignant prostatic epithelium and in a subset of non-prostatic tissues. In prostate cancer, PSMA expression has been shown to correlate with disease progression, with highest levels expressed in hormone-refractory metastatic disease. PSMA expression has also been reported on the neovasculature of a variety of non-prostatic solid tumors. In anatomic pathology PSMA is used in the identification of prostate origin of metastatic neoplasms. The pattern of expression of PSMA is membranous, with a dimmer cytoplasmic component. |
| 2081 |
PTEN (138G6) |
Phosphatase And Tensin Homolog, |
88342 |
Endometrial carcinoma is the most common malignancy of the female genital tract. It is a heterogeneous disease that has traditionally been divided into type 1 and type 2 cancers. Type 1 tumors are low grade endometrioid carcinomas and are generally associated with good clinical outcomes. In contrast, type 2 tumors are high grade, serous, clear cell, undifferentiated or poorly differentiated endometrioid carcinomas which have an aggressive clinical course and hormone-independent pathogenesis. Type 1 tumors are typically associated with microsatellite instability and mutations in PTEN, K-RAS and CTNNB1. Type 2 endometrial carcinomas often show p53 mutations. Both type 1 and type 2 endometrial carcinomas can have PIK3CA mutations, and these can coexist with mutations in PTEN and p53 respectively. PTEN loss is also detected in 30–50% of sporadic endometrial cancers and has been shown to occur through both genetic and epigenetic mechanisms. |
| 2082 |
PTH (MRQ-31) |
Parathyroid Hormone |
88342 |
The parathyroid glands function within the endocrine system to promote blood calcium homeostasis through controlled release of parathyroid hormone (PTH). This process involves the synthesis and secretion of PTH by activated parathyroid chief cells during conditions of hypocalcemia. With the anatomical proximity to the thyroid and capacity of associated neoplasms of the parathyroid to mimic thyroid tumors, challenges can arise in distinguishing between these types of abnormalities. In cases where there is uncertainty about a tumor being of parathyroid origin, immunohistochemical evaluation using anti-PTH can be of value. |
| 2083 |
PU.1 (9G7) |
SPI1, SPI-A, SFPI1 |
88342 |
PU.1 is a transcriptional activator and ETS oncogene family member based on similarity to the v-ets oncogene from the avian retrovirus E26 which causes erythroid and myeloid leukemias in chickens. PU.1 is highly expressed in cells of myeloid and B-lymphoid origin with absent expression in a number of non-hematopoietic tissues. By ISH, expression in myeloid elements include, early but not mature granulocytic and erythroid cells, megakaryocytes, monocytes, histiocytes and dendritic cells. Potential utility of PU.1 in the diagnosis of histiocytic sarcomas and other histiocytoses has been raised. The nuclear localization can be helpful to more clearly identify tumor cells. The expression in B-cell lymphomas has also been evaluated with potential utility in distinguishing nodular lymphocyte predominant Hodgkin lymphoma in challenging cases. It is positive in NLPHL and negative in classic Hodgkin lymphoma and anaplastic large cell lymphoma. |
| 2084 |
Rb1 (G3-245) |
Retinoblastoma Protein, Rb |
88342 |
Retinoblastoma gene/protein is a tumor suppressor gene at 13q14. Encodes a 110-114 kDa nuclear protein that plays a crucial role in cell cycle progression by regulating cell cycle arrest at G1-S. Somatic mutations can cause various tumors and aberrant/loss of Rb1 expression has been reported in the following tumors: poorly differentiated neuroendocrine carcinoma, mammary type myofibroblastoma, cellular angiofibroma, genital stromal tumor, spindle cell lipoma and superficial acral fibromyxoma. Therefore, aberrant/loss of Rb1 expression can be helpful to establish these diagnoses. |
| 2085 |
S100 (P) |
S100 Calcium Binding Protein |
88342 |
S100 antibody labels cells expressing S100 and is a useful aid for the classification of neoplasms, such as malignant melanoma, Langerhans' histiocytosis, chondroblastoma, and schwannoma. Differential classification is aided by the results from a panel of antibodies. S100 is a multigene family of low molecular weight (Mr between 9 000 and 13 000) Ca2+-binding proteins. The family comprises 19 members that are differentially expressed in a large number of cell types. Thus, S100B (previously S100β) is most abundant in glial cells of the central and peripheral nervous system, in melanocytes, chondrocytes, and adipocytes, whereas S100A1 (previously S100A/S100α) is most abundant in cardio-myocytes, slow twitch skeletal muscle cells, salivary epithelial cells, and renal cells. Additionally, S100B has been found in tumor cells and subpopulations of neurons, while S100A1 has also been detected in hippocampal neurons. S100A6 is expressed by fibroblasts and smooth and heart muscle cells. |
| 2086 |
SALL4 (6E3) |
DRRS, HSAL4, MGC133050, ZNF797, Dj1112f19.1 |
88342 |
Sal-like protein 4 (SALL4) is a zinc finger-containing transcription factor that belongs to the Spalt/Sal transcription factor family. It has been known as a stem cell marker because of its role in the maintenance of self-renewal and pluripotency of embryonic stem cells. Recently, SALL4 is recognized as a novel germ cell marker. Immunohistochemical (IHC) studies indicate that SALL4 is a sensitive and specific diagnostic marker for primary germ cell tumors especially yolk sac tumors. Earlier markers used for diagnosing primary germ cell tumors include placental-like alkaline phosphatase, C-KIT, CD30 and α-fetoprotein. Although these are good markers, they only show moderate sensitivity and/or specificity. More recently, novel stem cell markers, OCT4, NANOG, and SOX2 have been proposed as more sensitive makers, but they were expressed only in a subset of primary germ cell tumors, such as seminomas, intratubular germ cell neoplasias (ITGCN) and embryonal carcinomas, whereas other types of germ cell tumors, yolk sac tumors for example were not immunoreactive for these markers. Among the germ cell tumors, yolk sac tumor poses the greatest diagnostic challenges because of its multiple histological patterns. SALL4 has been reported to have 100% sensitivity for yolk sac tumors, seminomas, ITGCNs and embryonal carcinomas. Here we developed a protocol for SALL4 IHC stain and verified its usage in diagnosis of germ cell tumors. |
| 2087 |
SATB2 (EP281) |
Special AT-rich sequence binding protein 2 |
88342 |
Special AT-rich sequence-binding protein 2 (SATB2) binds specifically to nuclear matrix attachment regions of DNA. It functions as a transcriptional regulator and is involved in chromatin remodeling. Recently, SATB2 has been identified as a sensitive and specific marker of colorectal epithelium. SATB2 expression was found in 78.7% of lower gastrointestinal (GI) malignancies, but it was negative in the majority of upper GI (88.5%), primary ovarian neoplasms (98.3%), and primary ovarian carcinomas (95%). The distinction between primary ovarian mucinous tumors and colorectal neoplasms metastatic to ovary is challenging, adding SATB2 Immunohistochemistry (IHC) to the existing markers would aid diagnosis. Here we developed a SATB2 IHC stain and validated its usefulness in distinguishing ovarian metastases of colorectal origin form primary ovarian tumors of mucinous and endometrioid type. SATB2 is also a marker of osteoblastic differentiation, and can be used to help distinguish hyalinized collagen from osteoid matrix. The antibody’s specificity in this situation, however, may be limited. |
| 2088 |
SDHA (2E3GC12FB2AE2) |
Succinate Dehydrogenase A, Succinate dehydrogenase complex flavoprotein subunit |
88342 |
Succinate dehydrogenase (SDH), also known as or succinate-coenzyme Q reductase or respiratory Complex II, is a heterotetrameric enzyme complex located in the inner mitochondrial membrane and participates in both the citric acid cycle and the respiratory chain. SDH is composed of four subunits: two hydrophilic (A and B) and two hydrophobic (C and D). The SDH subunit A (SDHA) is a flavoprotein and contains a covalently attached flavin adenine dinucleotide (FAD) cofactor and a succinate binding site. It is responsible for conversion of succinate to fumarate. Subunit B (SDHB) is an iron sulphur protein that participates in the electron transport chain for the oxidation of ubiquinone to ubiquinol. Subunits C and D (SDHC and SDHD) are membrane-anchoring subunits. Loss of function of the SDH complex characterizes a rare group of human tumors including a subset of gastrointestinal stromal tumors (GIST), paragangliomas, renal cell carcinomas (RCC). |
| 2089 |
SDHB (EPR13042B) |
Succinate Dehydrogenase B |
88342 |
Succinate dehydrogenase (SDH), also known as or succinate-coenzyme Q reductase or respiratory Complex II, is a heterotetrameric enzyme complex located in the inner mitochondrial membrane and participates in both the citric acid cycle and the respiratory chain. SDH is composed of four subunits: two hydrophilic (A and B) and two hydrophobic (C and D). The SDH subunit A (SDHA) is a flavoprotein and contains a covalently attached flavin adenine dinucleotide (FAD) cofactor and a succinate binding site. It is responsible for conversion of succinate to fumarate. Subunit B (SDHB) is an iron sulphur protein that participates in the electron transport chain for the oxidation of ubiquinone to ubiquinol. Subunits C and D (SDHC and SDHD) are membrane-anchoring subunits. |
| 2090 |
SF-1 (N1665) |
Steroidogenic Factor 1, NR5A1, AD4BP, FTZ-F1 |
88342 |
Steroidogenic factor 1 (SF-1), is a nuclear hormone receptor that plays an important role in steroidogenesis, development of gonads and adrenal glands, sexual differentiation and reproduction. SF-1 is expressed in all the major steroidogenic tissues such as adrenal cortex, testes and ovaries. Recent studies suggest that SF-1 is a useful marker in distinguishing adrenocortical tumors from renal neoplasms. We developed a protocol for performing SF-1 IHC staining and validated its usage in aiding the differential diagnosis of various types of renal tumors versus adrenocortical tumors, including adrenal cortical adenoma and adrenocortical carcinoma. |
| 2091 |
SMAD4 (EP618Y) |
DPC4, MADH4, Deletion Target In Pancreatic Carcinoma 4 |
88342 |
SMAD4 (mothers against decapentaplegic homolog 4 drosophila) is a tumor suppressor gene that plays a critical role in the transforming growth factor-beta (TGF-beta) signaling pathway, which regulates cellular proliferation, differentiation, and apoptosis. Normally, SMAD4 is expressed within the nucleus of epithelial cells, while loss of SMAD4 expression is caused by inactivation of the SMAD4 gene due to sporadic genetic variants. Loss of SMAD4 expression is commonly observed in several types of cancer, including adenocarcinoma of the pancreas. It is associated with a more aggressive tumor phenotype and poorer prognosis. One of the mechanisms by which loss of SMAD4 expression contributes to adenocarcinoma development is through dysregulation of TGF-beta signaling. Normally, TGF-beta signals through SMAD proteins, including SMAD4, to inhibit cell proliferation and promote differentiation. In the absence of SMAD4, TGF-beta signaling can become disrupted, leading to uncontrolled cellular growth and proliferation. |
| 2092 |
SMARCA2 (P) |
BRM, SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily A, Member 2 |
88342 |
SMARCA2, also known as BRM (Brahma) is an important catalytic component of the SWI/SNF chromatic remodeling complex. Loss of expression of SMARCA2 has been observed in small cell carcinoma of the ovary. Undifferentiated carcinomas of the gastrointestinal tract and gynecological tract are rare malignancies with variable rhabdoid features that are defined as malignant epithelial tumors. Further characterization of these tumors have shown that they demonstrate loss of the SWI/SNF complex protein expression which include the subunits SMARCB1, SMARCA2, SMARCA4, and ARID1A. Therefore, the ability to demonstrate SMARCA2 loss of expression within these rare tumor subtypes is helpful in establishing a diagnosis and understanding of the pathogenesis of these tumors. |
| 2093 |
SMARCA4 (EPNCIR111A) |
BRG1 |
88342 |
SMARCA4, also known as BRG1, is a component of the SWI/SNF chromatin remodeling complex which alters DNA-histone contacts with a nucleosome in an ATP-dependent manner. The SWI/SNF complex also functions as a tumor suppressor by regulating transcription and cell differentiation. SMARCA4 is widely expressed in most tissues, but inactivation of the SMARCA4 gene leading to loss of SMARCA4 protein expression has been reported in several aggressive tumors including small cell carcinoma of the ovary, hypercalcemic type (SCCOHT) and undifferentiated thoracic sarcomas with characteristic rhabdoid morphology. SMARCA4 deficiency has also been reported in a subset of carcinomas arising in the endometrium, gastrointestinal tract, and lung. Identification of SMARCA4 deficiency assists in the differential diagnosis of these uncommon neoplasms. |
| 2094 |
SMMS1 (SMMS1) |
Smooth Muscle Myosin Heavy Chain |
88342 |
SMMS-1 is a mouse monoclonal antibody that highlights the myoepithelial cell layer. The absence of a myoepithelial cell layer aids the pathologist in determining the invasive nature of a breast lesion. SMMS-1 is an important sensitive and specific marker for myoepithelial cells as it stains the cytoplasm of the cells. Useful as an adjunct to p63, a nuclear stain, it has long been noted that a combination of IHC stains be used in evaluating myoepithelial cells as the presence or absence determines in situ or invasive carcinoma. |
| 2095 |
SOX-10 (BC34) |
SRY-related high-mobility group HMG box gene 10 |
88342 |
SOX10 (SRY-related high-mobility group HMG box gene 10) protein is a nuclear transcription factor. SOX10 acts as a nucleocytoplasmic shuttle protein and is essential for the survival of neural crest-derived cells and for the maintenance of the multi-potency of neural crest cells. Neural crest-derived cells include neurons and glial cells in the peripheral nervous system, melanocytes of the skin, C-cells of the thyroid, catecholaminergic cells of the adrenal gland, and cartilage and bone of the face. Immunohistochemistry study showed SOX10 expression in Schwann cells of the peripheral nerves, oligodendrocytes of the cerebral cortex, melanocytes of the epidermis, mast cells, acinar cells in the salivary glands, and myoepithelial cells of the submucosal bronchial glands, salivary glands, and breast. The restricted distribution of SOX10 protein indicates that immunohistochemical stain (IHC) of this protein may be useful in diagnosis of tumors originating from neural crest-derived cells. Recent studies have demonstrated that SOX10 is a sensitive marker for melanoma as well as for nerve sheath tumors. We developed a SOX10 IHC protocol and validated its use in aiding the diagnosis of melanoma and nerve sheath tumors including neurofibroma and Schwannoma. |
| 2096 |
SOX-11 (MRQ-58) |
SRY (sex determining region Y)-box 11 |
88342 |
Mantle cell lymphoma (MCL) is an aggressive disease and accounts for 5 to 10% of B-cell lymphomas. Distinction of MCL from its morphologic mimics is important for appropriate therapy and prognosis. CD5, CD10, CD23, and cyclin D1 have been used as major markers for MCL diagnosis. Recently, SOX11, a transcription factor, has been suggested to function as an oncogene in MCL. |
| 2097 |
SS18-SSX (E9X9V) |
Synovial sarcoma translocation, chromosome 18 fusion protein |
88342 |
The SS18-SSX fusion proteins results from in-frame fusions of the SS18 gene on chromosome 18 with X chromosome genes SSX1, SSX2, and SSX4. Synovial sarcoma is a soft tissue malignancy with poor prognosis in which 95% harbor recurrent translocation of the SS18 gene on chromosome 18. Accurate diagnosis of synovial sarcoma is important for appropriate clinical management of patients. Studies have shown that the SS18-SSX fusion in synovial sarcoma and therefore identification of this fusion protein is diagnostic. The SS18-SSX fusion specific antibody for immunohistochemistry would provide to be a useful tool for the diagnosis of synovial sarcoma based on histologic features and prior to known genetic confirmation of SS18-SSX gene fusion by fluorescence in situ hybridization. The SS18-SSX fusion protein does not cross-react with wild-type SS18 or SSX proteins. |
| 2098 |
SSTR2A (UMB1) |
Somatostatin Receptor 2 |
88342 |
Expressed in many cell types, somatostatin receptor 2A (SSTR2A) is coupled via pertussis toxin sensitive G proteins to inhibition of adenylyl cyclase. It also stimulates phosphotyrosine phosphatase and PLC via pertussis toxin insensitive as well as sensitive G proteins. SSTR2A is the functionally dominant somatostatin receptor in pancreatic islets. SSTR2A expression is found in a variety of neuroendocrine and other tumor types. Diagnostically, SSTR2A expression is useful in the differential diagnosis of meningiomas as the majority of meningiomas are known to be positive for SSTR2A while mimics such as Schwannomas are reported to be negative. |
| 2099 |
SSX (E5A2C) |
Synovial Sarcoma, X |
88342 |
The SSX antibody recognizes endogenous levels of total SSX1-4 proteins and can detect the SS18-SSX fusion protein. SS18-SSX fusion proteins results from in-frame fusions of the SS18 gene on chromosome 18 with X chromosome genes SSX1, SSX2, and SSX4. Synovial sarcoma is a soft tissue malignancy with poor prognosis in which 95% harbor recurrent translocation of the SS18 gene on chromosome 18. Accurate diagnosis of synovial sarcoma is important for appropriate clinical management of patients. Studies have shown that the SS18-SSX fusion in synovial sarcoma and therefore identification of this fusion protein is diagnostic. The detection of SSX protein by immunohistochemistry, in conjunction with morphology provides adjunctive support for the diagnosis of synovial sarcoma. |
| 2100 |
STAT6 (YE361) |
Signal transducer and activator of transcription 6 |
88342 |
Differentiating solitary fibrous tumour (SFT) from other benign mesenchymal tumors is difficult. The recently discovered NAB2-STAT6 translocation is present in most cases of SFT and results in the expression of a fusion protein in which the repressor domain from NAB is replaced by the transactivation domain from the carboxy terminal of STAT6. This fragment of STAT6 can be detected by immunohistochemistry, which could be an effective surrogate for more expensive fluorescence in-situ hybridization. STAT6 does not cross-react with other STAT family members. |
| 2101 |
SV40 (Pab101) |
SV40 large T-antigen/Simian Virus 40/Anti-SV40 T Antigen |
88342 |
Polyomavirus-associated nephropathy (PVAN) is an emerging disease in renal transplant patients with impaired T-cell immunity. BK virus (BKV) is the primary etiological agent, but JC virus (JCV) and possibly simian virus 40 (SV40) may account for some cases. The clinical challenge is to differentiate the viral interstitial nephritis caused by BKV from acute cellular rejection because treatment for infection is the opposite of treatment for rejection, and the conditions are histologically indistinguishable. The importance arises because the SV40 T antigen is a common antigen to all three polyomaviruses. |
| 2102 |
Synaptophysin (SYP/3551) |
SYP, MRX96, Major Synaptic Vesicle Protein P38 |
88342 |
Synaptophysin, a 38 kD glycoprotein, is the major integral membrane protein of synaptic vesicles. Major concentrations of the protein are found in the trans-Golgi region, in the presynaptic vesicles of neurons (brain, spinal cord, retina, neuromuscular junctions), and the smooth-surfaced vesicles of neuro-endocrine cells of the gut, adrenal medulla, pancreatic islets, and pheochromocytomas. Synaptophysin is a sensitive quantitative molecular marker of synaptic density and also a useful marker in the identification and characterization of neuronal and neuroendocrine neoplasms of the adrenal medullary, pituitary, thyroid, islet cell tumors, gastrointestinal, bronchial, thymic, and pancreatic carcinoid tumors. Immunohistochemistry of synaptophysin has been used in the evaluation of functional bowel disorders, cortical epileptogenesis, schizophrenia, and amyotrophic lateral sclerosis. |
| 2103 |
Syph (T.Pallidum) (P) |
SPIROCHETE, T. PALLIDUM |
88342 |
Treponema pallidum (Spirochete) is the causative agent of syphilis. Treponema pallidum can now be successfully localized with immunohistochemical techniques in formalin-fixed paraffin-embedded tissue. Studies have shown this offers a substantial advantage over silver-techniques in both sensitivity and specificity. |
| 2104 |
Tau (P) |
Tau protein |
88342 |
Detection of neurofibrillary tangles and amyloid pathology are required for the diagnosis of Alzheimer’s disease. Both tangles and plaques may be detected by histochemical stains or by immunohistochemistry. Guidelines published by the National Institute of Aging and Alzheimer’s Association recommend that IHC analysis be used for the detection of plaques and tangles rather than histochemical analyses, such as Thioflavin S or Bielschowsky stains. |
| 2105 |
TCL-1A (1-21) |
T-cell leukemia/Lymphoma Protein 1A |
88342 |
T-cell leukemia/Lymphoma Protein 1A (TCL1A), also known as p14TCL1 is a product of the TCL1 gene that is involved in T-cell prolymphocytic leukemia (TPLL). T-PLL is a rare form of mature T-cell leukemia, which is consistently associated with chromosomal rearrangements characterized by the juxtaposition of the TCRA locus on chromosome 14q11 and the TCL1A gene on 14q32.13. TCL1A is expressed in pre-B cells, in immature thymocytes, at low levels in activated T cells, and in the cytoplasm |
| 2106 |
TCR beta F1 (8A3) |
T Cell Receptor Beta Locus F1 |
88342 |
The T cell immune receptor consists of a heterodimer comprising the antigen recognition chains and the invariant CD3 complex. Approximately 85% of T cells contain the alpha/beta heterodimer, the other 15% bear the gamma/delta heterodimer. The γδ T-cells are most common in epithelial sites and may represent a more primitive form of T-cell, corresponding with the lesser degree of genetic diversity on the γ and δ gene loci compared to α and β loci. Lymphoid proliferations of T-cell phenotype may be derived from either αβ or γδ T-cells. Classification of certain uncommon types of lymphomas such as hepatosplenic T-cell lymphomas and cutaneous γδ T-cell lymphomas require demonstration of T-cell receptor type. NK cell neoplasms, while containing CD3ε lacks antigen binding heterodimers. |
| 2107 |
TCR delta (H-41) |
T cell antigen receptor δ |
88342 |
Gamma-delta T-cells are a subset of CD3 positive CD4/CD8 negative T-cells with a relatively poorly understood function. While they mature in the thymus like their alpha-beta counterparts, they appear to recognize multiple antigens including self and non-self proteins, lipids and phosphorylated isoprenoids. They appear to respond rapidly to developmentally pre-programed stimuli and their functions do not appear to require clonal expansion. They interact with major immune cell subsets and their major role appears to be the response to specific pathogens, mainly infectious. The mature gamma-delta T-cells reside in the target organs, they are the most abundant in the intestinal tract, spleen, placenta. Lymphomas with a gamma-delta T-cell immunophenotype are rare but aggressive: hepatosplenic T-cell lymphoma, primary cutaneous gamma-delta T-cell lymphoma. The gamma-delta T-cells are detected mainly by flow cytometry, but immunohistochemical methods are also being developed. They are negative for the alpha-beta T-cell receptor specific antibody betaF1. |
| 2108 |
TdT (SEN28) |
Terminal Deoxynucleotidyl Transferase |
88342 |
TdT is overexpressed in B- and T-cell acute lymphocytic leukemias (ALL) and in a subset acute myeloid leukemias (AML) including AML with minimal differentiation. About 90% of patients with ALL show variable levels of TdT expression as well as multiple isoforms of TdT in their blast cells. The frequency of TdT overexpression in AML is less (~20%), and it is negative in most mature lymphoid malignancies such as chronic lymphocytic leukemia. A subset of aggressive B-cell lymphomas may express TdT creating potential diagnostic challenges. It has also been reported in the setting of blastic transformation of mantle cell lymphoma. |
| 2109 |
Thyroglobin (P) |
Tg |
88342 |
This antibody labels thyroglobulin in thyroid tissue and is a useful aid for the classification of well differentiated thyroid carcinomas. Thyroglobulin (Tg) is a glycoprotein with a predominant form as a 660 kDa homodimer. Tg, the precursor of thyroid hormones, is synthesized by thyrocytes and transported to the apical surface where it is secreted into the lumen of thyroid follicles and stored as the major component of colloid (> 95%). A minor proportion of Tg is found as 330 kDa monomers or as tetramers. Reduction or degradation of 660 kDa or 330 kDa Tg molecules can lead to the formation of smaller polypeptides, some of which are present in trace amounts in the colloid. At the cell-colloid interface, post-transitional modifications of Tg occur, which are characterized by coupling of tyrosyl residues with iodide, leading to the formation of thyroid hormone residues within the Tg molecule. Hormone release generally requires uptake of Tg from the colloid by thyrocytes and proteolytic cleavage along the lysosomal pathway. Antibody to thyroglobulin has been shown to be useful in positive identification of thyroid carcinomas of the papillary and follicular types. Demonstration of thyroglobulin in a metastatic lesion establishes the thyroid origin of the tumor. Adenocarcinomas of non-thyroidal origin are not reactive. |
| 2110 |
TIA (TIA-1) |
T cell intracytoplasmic antigen |
88342 |
TIA-1 (T-cell intracytoplasmic antigen) monoclonal antibody reacts with a 15 kDa cytoplasmic granule-associated protein, expressed in lymphocytes processing cytolytic potential. The expression of TIA-1 was studied in CD30+ anaplastic large cell lymphomas (ALCL), NK-cell lymphomas and peripheral T-cell lymphomas and T-cell lymphocytosis, B-cell lymphomas and lymphoblastic leukemia, Hodgkin's etc. Studies showed that 60 to 70% of anaplastic large cell lymphoma reacted with TIA-1. Studies also indicate that TIA-1 reacts with most large granular lymphocytic leukemia's, hepatosplenic T-cell lymphomas, intestinal T-cell lymphomas, NK-like T-cell lymphomas, NK-cell lymphomas, nasal T/NK-cell lymphomas, subcutaneous T-cell lymphomas, pulmonary angiocentric lymphomas of T-or NK-phenotype. The author concluded from TIA-1 studies that anaplastic large-cell lymphomas are cytotoxic T-or NK-cell neoplasms. All B-cell lymphomas, Hodgkin's and lymphoblastic leukemia's were negative for TIA-1. |
| 2111 |
TLE-1 (1F5) |
Transducin-like enhancer split-1 |
88342 |
Transducin-like enhancer of split 1 (TLE1) gene is a member of the TLE gene family and involved in control of hematopoiesis, neuronal, and terminal epithelial differentiation. By immunohistochemistry in formalin-fixed, paraffin-embedded tissues, TLE1 expression (nuclear staining) has been found in 35 of 35 molecularly confirmed synovial sarcoma cases, and was rare to absent in the 73 other soft tissue tumors examined (positive staining was found only in 1 of 43 malignant peripheral nerve sheath tumors and 1 pleomorphic sarcoma). Anti-TLE1 was more sensitive and specific for synovial sarcoma than other currently available immunohistochemical markers including BCL2, epithelial membrane antigen and cytokeratins, and had a positive predictive value of 92% and a negative predictive value of 100% in this clinical setting. TLE1 overexpression by immunohistochemistry is a highly sensitive and specific biomarker for the diagnosis of synovial sarcoma in the group of otherwise unclassifiable high-grade sarcomas. |
| 2112 |
Tpit (CL6251) |
TBX19, T-Box Transcription Factor 19 |
88342 |
Tpit (T-box family member TBX19) regulates the proopiomelanocortin (POMC) lineage giving origin to the corticotrophs within the pituitary gland. The nuclear expression of the pituitary specific transcription factors such as Tpit within pituitary tumors cells that are differentiated towards a respective pituitary cell lineage serves as a useful complement in the classification of pituitary neuroendocrine tumors. Therefore, distinct nuclear labeling for Tpit antibody within pituitary tumors can precisely classify pituitary neuroendocrine tumors by cell lineage. |
| 2113 |
Transthyretin (BSB-125) |
Prealbumin, TTR |
88342 |
Transthyretin is used in the diagnosis amyloidosis, a progressive condition characterized by deposits of the protein amyloid in the body's organs and tissues. There are several types of systemic amyloidosis: primary (caused by monoclonal immunoglobulins); secondary (caused by amyloid A secondary to chronic inflammation); senile (wild type transthyretin); familial (mainly transthyretin, but multiple other proteins too). Localized amyloidosis can be composed of multiple other proteins including semegelin, atrial natriuretic hormone, as well as others. The stain for transthyretin can identify senile and familial amyloidosis. |
| 2114 |
TRPS1 (EP392) |
Transcriptional Repressor GATA Binding 1, LGCR |
88342 |
The trichorhinophalangeal syndrome 1 (TRPS1) gene belongs to the GATA transcription factor family. It is a specific gene for breast carcinomas including ER/PR positive luminal A and B tyles, HER2-positive type, and basal-type TNBC. TRPS1 has no or little expression in lung, pancreas, colon, and gastric adenocarcinomas; in addition to urothelial, renal, ovarian, or melanomas. Therefore, TRPS1 marker is a sensitive and specific marker for breast carcinoma, in particular TNBC. |
| 2115 |
Tryptase (AA1) |
TRYPTASE, MAST CELL |
88342 |
Human mast cell tryptases (EC 3.4.21.59) comprise a family of trypsin-like neutral serine proteases that are predominantly expressed in mast cells. In its enzymatically active form, mast cell tryptase exists as a non-covalently linked tetramer of 132 kDa. Mast cell tryptase is capable of degrading vasoactive intestinal peptide and activating prekallikrein as well as generating kinins, all important mediators involved in bronchoconstriction and airway hyperresponsiveness, which are major contributors to allergic airway disease. Mast cell tryptase also exhibits mitogenic effect on human airway smooth muscle cells, and human lung and dermal fibroblasts. Both smooth muscle hyperplasia and fibrotic changes can lead to thickening of the airway wall and a permanent reduction in airway caliber. Mast cells are activated by a number of stimuli, including antigen, superoxides, complement protein, neuropeptides and lipoproteins, resulting in activation and degranulation. Mast cell degranulation and thereby release of mast cell tryptase as well as histamine, leukotrienes and cytokines into the surrounding tissue is a pivotal event in an inflammatory response and seems to play an important role in host defense against pathogens. Mast cells play an active role in such diverse diseases as atherosclerosis, asthma, arthritis, bile duct fibrosis, malignancy and pulmonary fibrosis. Identification of mast cells through staining of tissues with antibodies specific for human mast cell tryptase has been useful in identification of focal and diffuse MC infiltrates in primary MC disease and mastocytosis. Demonstration of mast cell tryptase is essential for the identification of highly atypical, hypogranulated or even non-metachromatic MCs, especially in MC leukemia, and for the detection of small or minute MC infiltrates. |
| 2116 |
TSH (P) |
Thyroid stimulating hormone, thyrotropin |
88342 |
Anti-TSH is a useful marker in classification of pituitary tumors and the study of pituitary disease. It reacts with TSH-producing cells (thyrotrophs). |
| 2117 |
TTF-1 (8G7G3/1) |
Thyroid Transcription Factor 1 |
88342 |
Thyroid transcription factor 1 (TTF-1) is a 38 kDa nuclear protein member of the family of homeodomain transcription factors. TTF-1 expression was originally demonstrated in follicular cells of the thyroid gland and subsequently found in the respiratory cells of the lung. Expression in epithelial cells of the thyroid gland and lung allows TTF-1 to be a useful antibody for the classification of tumors arising in these organs. In context with other data, TTF-1 becomes useful in the investigation of metastatic adenocarcinomas of an unknown origin. Antibody to TTF-1 demonstrates an intranuclear staining pattern, and normal thyroid gland follicle cells and lung parenchymal alveolar lining cells serve as excellent tissue internal controls. |
| 2118 |
Tyrosinase (T311) |
TYR, OCAIA |
88342 |
Patient tissues are stained using the same conditions that were used in the validation study. The specificity of the interaction between the primary antibody or the nucleic acid probes and their targets allows confident identification of the targets in the tissue. This identification (or the confident diagnosis of absence) is of fundamental importance in the current diagnostic algorithms. The biosynthesis of melanin in melanocytes involves a family of enzymes, a key member of which is tyrosinase. Tyrosinase deficiency is associated with various forms of albinism and in particular oculocutaneous albinism. L-tyrosinase is the initial substrate for melanin biosynthesis and its conversion to dopaquinone is catalyzed by tyrosinase, whose expression is reported in melanocytes and melanomas. |
| 2119 |
Vimentin (V9) |
VIM |
88342 |
Vimentin reacts with the 57kD intermediate filament protein, vimentin. Vimentin is a single peptide that was initially isolated from chicken embryo fibroblasts. It is the major and usually only intermediate filament in a variety of non-muscle mesenchymal cells, including all fibroblastic cells, endothelial cells, lipocytes, Schwann cells and macrophages. Intermediate filaments are components of the cytoskeleton. Vimentin is not present in normal epithelial cells in vivo, although it has been described in epithelial cells in culture and may appear in the tumor cells of neoplasms (carcinoma). Vimentin has been reported to be present in hair follicles, and thought to be associated with melanocytes, while association with Langerhans cells or lymphocytes is a less likely possibility. The pattern of expression of intermediate filaments may be used as a device to aid in the classification of undifferentiated neoplasms. Vimentin is expressed in most malignant melanomas, either in the primary site or in metastatic foci. Vimentin has been observed to be the principal intermediate filament expressed in malignant fibrous histiocytoma and has been used as a marker to distinguish between this tumor and other soft tissue sarcomas. |
| 2120 |
WT1 (6F-H2) |
Wilms’ Tumor 1 |
88342 |
WT1 encodes a zinc finger transcription factor which encodes the early growth response (EGR-1) consensus sequence found in promoters of growth factor genes. WT1 is involved in the induction of Wilms’ tumor, a pediatric renal malignancy, and is normally expressed in glomerular epithelium of the kidney. Nuclear expression of WT1, as detected with an N-terminal antibody, may be seen in Wilms tumor, malignant mesothelioma, serous adenocarcinoma of the ovary and peritoneum, malignant melanoma and sex-cord stromal tumors. The mouse monoclonal antibody 6F-H2, directed against the N-terminal of WT1, was previously validated in the Immunohistochemistry laboratory using a concentrate manufactured by Dako. As the concentrate has been discontinued, this study is performed to evaluate the performance of the 6F-H2 monoclonal antibody purchased from Dako in a pre-dilute, ready-to-use (RTU) format. |
