Ovarian carcinoma: pathology review with an emphasis in their molecular characteristics

Ovarian carcinoma is highly aggressive and difficult to treat neoplasm, which is usually detected in advanced stages where most patients recur. Extensive investigation about several treatment modalities has been performed but this neoplasm has poor benefits from such treatments including targeted therapy. Recent data have begun to highlight the histological and molecular heterogeneity of these tumors defining this neoplasm, not as a single disease but a group of heterogeneous histological subtypes with important differences in terms of genetics, morphology, oncogenesis, prognosis, chemosensitivity and especially molecular characteristics that are likely to be targets of new molecules. In general, high-grade serous carcinomas are characterized by great genomic instability and frequent amplifications and deletions; lowgrade ovarian neoplasms are genomically stable. On this phytopathogenic basis, recent findings suggest a dual model of carcinogenesis consisting of two large groups named types I and II. Type I cancers (serous, mucinous, and low-grade endometrioid) commonly arise from well-described, genetically stable precursor lesions (usually borderline tumors); manifests as large adnexal masses with the early-stage disease, and they have a good overall prognosis. In contrast, type II carcinomas (serous, high-grade endometrioid, mixed, and undifferentiated carcinomas) originate de novo from the adnexal epithelium, often demonstrate chromosomal instability, and have aggressive biological behavior. Surprisingly, most of the genomic abnormalities detected encode known oncogenic proteins for which there is targeted therapy. Then, there is a real potential for personalized medicine adapted to the molecular portrait of tumors. In this review, I synthesize the histology and molecular pathology of ovarian carcinomas and possible strategies to reach targeted therapy.