Molecular Oncology of Gynecologic Tumors.

Oncologists and pathologists alike have recognized that the broad histologic categories, especially for ovarian and endometrial carcinomas, do not reliably segregate groups with similar clinical courses or responses to therapeutic interventions. During the last decade a paradigm shift was invoked when the results from The Cancer Genome Atlas (TCGA) project were published. Comprehensive genomic profiling data from TCGA has shown that there are four molecular subgroups of endometrioid carcinomas instead of the two subtypes proposed by Bokhman in the 1970s. For ovarian carcinomas (OC) it is now evident that molecular parameters are also significant. Although traditionally referred to as a single entity, OC is not a homogeneous disease but rather a group of diseases, each with different morphology and biologic behavior. Similar to endometrial cancers, advanced cervical cancer and recurrent disease remain particularly problematic due to chemotherapy resistance. Effective prophylactic vaccines against the most important carcinogenic human papillomaviruses (HPV) types are available, but uptake remains poor. The E6 and E7 oncoproteins are attractive targets for cancer therapy. They are constitutively expressed in HPV-positive tumors, specific to the tumor, functionally important to the tumor cells and recognized by the adaptive immune system as tumor antigens. This review summarizes recent advances in the molecular pathology, which have greatly improved our understanding of the biology of gynecologic cancers.