Biomarkers in Gynecologic Carcinomas

Morphological examination of the tumors is the gold standard for diagnosis of the gynecologic tract carcinomas. However, adjunct biomarkers are increasingly utilized in routine pathology practice for the purposes of differential diagnoses and better histologic subclassification of gynecologic tumors as well as to reveal prognostic/predictive and therapeutic benefits for specific treatments. The most commonly used ancillary method is immunohistochemistry (IHC), however, in situ hybridization (ISH) and molecular analysis also have been increasingly used. In general, cytokeratin profile (CK7, CK20), EMA (epithelial membrane antigen), PAX8 (Mullerian marker), ER (estrogen receptor), PR (progesterone receptor), WT1, p53, p16, IMP3, Ki-67, MMR proteins (MLH1, PMS2, MSH2, MSH6), Napsin A, HNF1β, AMACR, CDX2, SMAD4/DPC4, mCEA, vimentin, SALL4, inhibin-alpha, and calretinin are the most commonly used immunohistochemical stainings for the abovementioned purposes in daily practice. ISH studies, particularly to detect HPVs (human papilloma virus), are also important. This chapter discusses the utilities and pitfalls of the widely used immunohistochemical staining biomarkers in the context of overlapping morphological features observed in the ovary, fallopian tube, endometrium, cervix, and vulva-vagina carcinomas. Basically, primary carcinomas of these organs and their differential diagnoses have been considered and are summarized in the context of current tumor classification and molecular alterations.