Category: IHC-Antibodies

Anaplastic lymphoma kinase (ALK) belongs to the insulin receptor superfamily acting as a transmembrane receptorprotein-tyrosine kinase. In normal tissues, ALK protein is expressed only few cells within the developing and mature nervous system. ALK can be active in cancer through multiple mechanisms. The most common mechanism is through the formation of a fusion protein from chromosomal translocations. The protein expression by tumor cells is an independent prognostic factor that predicts a favorable outcome. ALK staining is positive in 50-60% of anaplastic large cell lymphoma (ALCL). NSCLC is found to express ALK 3-7%.

AMACR, also known as P504S or alpha-methylacyl-CoAracemase, is an essential enzyme in the b-oxidation ofbranched-chain fatty acids and their derivatives. The enzyme is expressed in mitochondria and peroxisomes of numerous tissues such as liver, biliary tract, kidney and lung. AMACR is overexpressed in patients with prostate cancer compared to benign tissue. Highest expression is found in localized prostate cancer and decreases as soon as the carcinoma forms metastases. It therefore makes sense to use AMACR as a biomarker for the aggressiveness of a prostate carcinoma and its course. The antibody may be particularly helpful in the panel with HMW cytokeratin and/or p63.

Arginase (ARG) is a manganese metalloenzyme that is part of the urea cycle. It catalyses the conversion of L-arginine to L-ornithine and urea. ARG-1 and ARG-2 are the two isoforms of ARG. ARG-1 is a cytosolic enzyme expressed in liver. The ARG-1 antibody is a sensitive marker of hepatic differentiation and is useful in the detection of hepatocytes in normal tissue as well as granulocytes in peripheral blood. For the identification of hepatocellular carcinoma ARG-1 is a sensitive and specific marker.

Bcl6 is a regulatory gene encoding a zinc finger protein. It plays a key role in the formation of the germinal center (GC) and acts as a regulator of B lymphocyte growth and development by protecting GC-B cells from DNA damage-induced apoptosis. Bcl-6 is mainly expressed in GC-B cells. Surrounding mantle-zone and marginal-zone B cells, plasma cells, and progenitor B cells are negative for Bcl-6. The antibody Bcl-6 detects GC cells in lymphoid follicles and a variety of lymphomas including follicular lymphomas, diffuse large B-cell lymphomas (DLBCL) and Burkitt’s lymphomas. In contrast, Bcl-6 is not expressed in hairy cell leukemias, mantle cell or peripheral lymphomas. Bcl-6 is not restricted to the B cell line, but could also be detected in anaplastic large cell lymphoma. Furthermore, Bcl-6 is involved in mammary epithelial differentiation, which could play a potential role in carcinogenesis.

CD117, also known as c-Kit, encodes a receptor tyrosine kinase that is activated by its ligand stem cell factor (also known as mast cell growth factor). CD117 plays an important role in vital functions, such as homeostasis and melanogenesis. In normal tissues, expression is found in interstitial cells of Cajal, mast cells, melanocytes, various epithelia, testicular and ovarian interstitial cells, neurons of the central nervous system, immature myeloid cells, trophoblastic cells, fetal (but not mature) endothelial cells and fetal (but not mature) basal cells of the skin. CD117 does not occur in smooth muscle cells.
CD117 is a proto-oncogene. Mutations and overexpression are associated with several cancer types, including gastrointestinal stromal tumors (GIST) with 80 95% expression and seminoma with > 90% expression.
CD117 is expressed in around 15-30% of melanomas, although this can vary depending on the type of melanoma. About 30% of lung adenocarcinoma show expression of CD117.

Keratins are cytoplasmic intermediate filament proteins expressed by epithelial cells and their neoplasms. Cytokeratin 20 is a type I keratin mainly found in the gastric and intestinal mucosa. Antibody Cytokeratin 20 is useful in the detection of a variety of adenocarcinomas arising from epithelia, such as colorectal carcinomas, transitional-cell and Merkel cell carcinomas, gastric and pancreatic tumors. CK20 is often used in a panel with antibody Cytokeratin 7.

CD3 is a protein complex that is composed of five chains (gamma, delta, epsilon, zeta, eta) which associate with theT-cell receptor (TCR). CD3 is first expressed in the cytoplasm of developing T-cells, then as they mature it moves to the membrane. CD3e is a membrane protein that plays a role in TCR-CD3 complex assembly and signal transduction regulating T-cell proliferation, apoptosis and thymocyte development. CD3e immunostaining is only seen in T-cells. These predominantly occur in lymphatic organs such as thymus, lymph nodes and tonsils but are regularly also seen – at lower density – in many other tissue types. In malignant lymphomas, CD3 is a pan-T-cell lineage-restricted antigen, detected in 72-95% of the T-cell lymphomas. As B-cell lymphomas are mostly negative forCD3e, the antibody can be used to distinguish between T-cell and B-cell lymphomas.

Cyclin D1 plays an important role in control of cell cycle and cell proliferation by regulating cyclin-dependentkinases. Cyclin D1 is a proto-oncogen. Overexpression and nuclear accumulation is associated with various cancers including breast, colon and prostate cancer, melanoma and lymphoma. Cyclin D1 may be used to differentiate mantle cell lymphoma from other B cell lymphoma.

Keratins are cytoplasmic intermediate filament proteins expressed by epithelial cells. Cytokeratin 5 is a type II keratin. This antibody detects metastatic carcinoma in the pleura, epithelial mesothelioma, almost all squamous cell carcinomas, half of transitional carcinomas, many undifferentiated large cell carcinomas and undifferentiated large cell carcinomas. A cocktail of CK5, its corresponding partner CK14 and p63 is useful to detect the basal-likephenotype of breast carcinoma and to differentiate normal and prostate cancer.

CD79a (mb-1) is an integral membrane protein expressed early in B cell maturation and next to CD75b (B29) one of two polypeptide chains of the CD79 molecule.The dimer of CD79a/b has the function to transmit signals to the B cell receptor signaling complex into the cell for induction of B cell activation. The CD79a antibody is used as a marker for identification of normal and neoplastic B lymphocytes.

Keratins are cytoplasmic intermediate filament proteins expressed by epithelial cells. CK6 is a type II keratin constitutively expressed in distinct types of epithelia such as those in oral mucosa, esophagus, papillae of tongue and hair follicle outer root sheath.