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Cytotoxic T-Lymphocyte-Associated Protein 4 (CTLA-4) is a receptor on T helper cells that functions as an immune checkpoint and downregulator of immune responses. Mutations in CTLA-4 are associated with insulin-dependent diabetes mellitus, Hashimoto’s thyroiditis, Graves’ disease, systemic lupus erythematosus (SLE), celiac disease, primary biliary cirrhosis, thyroid-associated orbitopathy, multiple sclerosis, and other autoimmune diseases. The spliced variant of CTLA-4 in SLE is present in the patient’s serum. Haploinsufficiency of CTLA-4 causes the immune system disorder known as CTLA-4 deficiency or CHAI disease (CTLA-4 haploinsufficiency with autoimmune infiltration).
Cytokeratin 7 (CK7) is a type II keratin which is present in transitional, ductal, glandular, and biliary duct epithelial cells. Cytokeratin 7 is a useful marker for distinguishing between carcinomas of the lung, breast, endometrium, and urothelia (positive stain) from carcinomas of the colon and prostate (negative stain). Cytokeratin 7 is present in nearly all primary lung adenocarcinomas, and is a useful marker in the differential diagnosis of ovarian neoplasms. Anti-Cytokeratin 7 does not stain intermediate filament.
Cluster of Differentiation 13 (CD13) is a transmembrane protein that is overexpressed in both hematological and solid malignancies, including Acute Myeloid Leukemia (AML). Although hypogranular variants of AML are difficult to distinguish from other AML subtypes due to the morphology, the diagnosis of this variant is possible through using a panel of CD13, CD16, CD33, CD34, and CD117. Alternatively, a panel of CD13, CD34, CD43, CD68, CD117, CD163, lysozyme, and MPO is very useful for accurately diagnosing myeloid sarcoma and distinguishing it from large cell lymphoma, undifferentiated carcinoma, lymphoblastic lymphoma, malignant melanoma, Burkitt’s lymphoma, extra-medullary hematopoiesis, and inflammation. Since CD13 is expressed in both normal and neoplastic liver tissues, CD13 staining is useful for distinguishing between hepatocellular carcinoma and non-hepatocellular neoplasms.
The p16 (p16INK4A) protein is a cyclin-dependent kinase (CDK) inhibitor that plays an important regulatory role in the cell cycle. By controlling the transition between the G1 and S phases through regulation of retinoblastoma protein, p16 decelerates cellular differentiation and therefore acts as a tumor suppressor, making it the key marker in several human cancers including head and neck cancer, perianal lesions, melanomas, gliomas, lymphomas, and some types of leukemia. p16 is also clinically indicated in carcinomas of the esophagus, pancreas, lung, biliary tract, liver, colon, and urinary bladder.
p27, also known as p27Kip1, is a cyclin-dependent kinase inhibitor that binds to and inhibits cyclin-dependent kinases, thereby regulating progression from G1 to S phase. Decreased expression of p27 is linked to poor prognosis in renal cell carcinoma, colon carcinoma, small breast carcinomas, non-small cell lung carcinoma, hepatocellular carcinoma, multiple myeloma, lymph node metastases in papillary carcinoma of the thyroid, and is associated with a more aggressive phenotype of carcinoma in the cervix.