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| wdt_ID | TEST (CLONE, P - polyclonal) | SYNONYMS | CPT CODE | CLINICAL SIGNIFICANCE |
|---|---|---|---|---|
| 796 | 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. |
| 797 | 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. |
| 798 | 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. |
| 799 | 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 +). |
| 800 | Adenovirus (M58+M73) | Adenovirus type 2 + type 5 | 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. |
| 801 | 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 |
| 802 | 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 |
| 803 | 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. |
| 804 | 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. |
| 805 | 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. |
| 806 | 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. |
| 807 | 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. |
| 808 | 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. |
| 809 | 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. |
| 810 | 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. |
| 811 | 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. |
| 812 | 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. |
| 813 | 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. |
| 814 | 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) |
| 815 | 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. |
| 816 | 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. |
| 817 | 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. |
| 818 | 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). |
| 819 | beta-Amyloid (6F/3D) | 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. |
| 820 | 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. |