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Cluster of differentiation 44 (CD44) is a glycoprotein receptor for hyaluronic acid, which plays a fundamental role in cellular adhesion, stromal binding, migration, and cell-cell interactions. Studies have suggested that the CD44-hyaluronate interaction is central to tumor invasiveness. Positive staining with Anti-CD44 is implicated in a multitude of different cancer types, including breast, prostatic, renal cell, colonic, hepatocellular, and genitourinary carcinomas, as well as Non-Hodgkin’s Lymphoma, metastatic melanoma, gastric cancer, and some soft tissue tumors. It has also been demonstrated that there is a positive correlation between tumor progression and increased expression of CD44v, a high molecular weight CD44 isoform that has been described in epithelial cells. Given the expression of CD44 in a wide range of cancers, the most practical application of CD44 immunostaining is its use in discriminating between urothelial transitional cell carcinoma in situ from non-neoplastic changes in the urothelium.
Cytokeratin 18 (CK18) is present in simple, glandular, and transitional epithelial cells, but is absent in stratified epithelial cells. CK18 usually multimerizes with Cytokeratin 8, and Anti-Cytokeratin 18 is useful for detecting adenocarcinomas of simple and glandular epithelium origin, as well as poorly differentiated squamous carcinoma cells.
GATA3 is a transcription factor important in cell proliferation, development, and differentiation. GATA3 is mostly observed in breast and urothelial carcinomas, and rarely present in other cancers such as endometrial endometrioid adenocarcinoma. Among the breast carcinomas, GATA3 has a lower expression in luminal B subtype breast carcinoma. Studies have found GATA3 expression to be associated with ER (estrogen receptor), PR (progesterone receptor), and Her2 in breast cancer cases. Urothelial carcinomas stain positively for GATA3 in invasive or high grade tumors, therefore Anti-GATA3 is useful for carcinoma diagnosis when breast and bladder are plausible.
Ki-67 is a nuclear, non-histone protein that is expressed only during active phases of the cell cycle (G1, S, G2 and M), but not in the resting phases (G0 and G1 early phase). Although the antigen has also been associated with ribosomal RNA transcription, it is strongly linked to cell proliferation and has thus been indicated as an effective marker in grading the proliferation rate of tumors, including those of the brain, breast, cervix, and prostate.
p504s, also known as α-methylacyl coenzyme A racemase (AMACR), is an enzyme localized in the peroxisome and mitochondria, which functions in β-oxidation of branched chain fatty acids, as well as bile synthesis. AMACR has been clinically indicated as a tissue biomarker for prostate cancer and colorectal cancer, as well as high-grade prostatic intraepithelial neoplasia, a precursor lesion of prostate cancer. p504s overexpression has also been detected in a number of other cancers including ovarian, breast, bladder, lung, and renal cell carcinomas, lymphoma, and melanoma.
p53, also known as tumor protein 53 or TP53, is a tumor suppressor and transcription factor that functions in a number of anti-cancer activities including DNA repair, cell-cycle arrest, and apoptosis in response to DNA damage or other stressors. Mutations in p53 are linked to a number of malignant tumors, including those of the breast, ovarian, bladder, colon, lung, and melanoma. Anti-p53 staining has been used to detect intratubular germ cell neoplasia, and also to distinguish between uterine serous carcinoma and endometrioid carcinoma.
Podoplanin is a transmembrane mucoprotein specifically expressed in the endothelium of lymphatic capillaries, while remaining absent from the blood vasculature. The protein is co-localized with VEGFR3/FLT4 in normal skin and kidney. Anti-Podoplanin is useful in the identification of lymphangiomas, Kaposi’s sarcomas, epithelioid mesotheliomas, hemangioblastomas, seminomas, and some angiosarcomas which likely have lymphatic differentiation.
Prostate-Specific Antigen (PSA) is a serine protease of the kallikrein family, that is produced by the prostate epithelium and epithelial lining of the periurethral glands. Although considered prostate-specific, PSA has also been detected in breast tissue, breast tumors, endometrium, adrenal neoplasms, and renal cell carcinomas. Anti-PSA can be used for differentiating high-grade prostate adenocarcinoma from high-grade urothelial carcinoma, as well as for determining the prostatic origin of carcinomas in non-prostate tissues. Anti-PSA recognizes primary and metastatic prostatic neoplasms, but not tumors of nonprostatic origin, and can be useful as an aid to confirm prostatic acinar cell origin in primary and metastatic carcinomas.