With advances in immunohistochemical technology and growing knowledge of the molecular genetics of tumors, immunohistochemistry is playing an increasingly important role in providing genetic information for tumors. Specific chromosomal translocations can be demonstrated through detection of the protein product of one of the genes involved in gene fusion (such as BCL2, cyclin D, and ALK). Some mutations can be detected by (1) aberrant localization of the protein product (such as β-catenin and nucleophosmin), (2) abnormal accumulation of the protein product as a result of stabilization of the protein (such as p53), and (3) mutation-specific antibodies directed against the mutant protein (such as isocitrate dehydrogenase gene R132H mutation, epidermal growth factor receptor gene L858R and exon 19 deletion mutations, and BRAF gene V600E mutation). Gene deletion or loss of function can be demonstrated by the loss of immunostaining for the protein product (such as mismatch repair proteins in microsatellite-unstable tumors, E-cadherin in lobular carcinoma of the breast, and INI1 in rhabdoid tumors, atypical teratoid/rhabdoid tumors, and epithelioid sarcomas). Gene amplification can be demonstrated by overexpression of the protein product (such as HER2 in breast and gastric cancers, and MDM2 or CDK4 in well-differentiated/dedifferentiated liposarcomas). Viruses associated with tumors can be demonstrated directly (such as Epstein-Barr virus latent membrane protein-1 in Hodgkin lymphomas, human herpesvirus 8 in Kaposi sarcomas, and Merkel cell polyomavirus in Merkel cell carcinomas) or by a surrogate marker (such as p16 in human papillomavirus infection). In this review, examples are given to illustrate the principles and pitfalls of these applications.
Keywords: chromosomal translocation; gene amplification; gene deletion; gene mutation; immunohistochemistry; molecular genetics; mutation-specific antibody; tumors; virus.