Challenges and Opportunities in Studying the Epidemiology of Ovarian Cancer Subtypes

Jennifer Anne Doherty, Lauren Cole Peres, Chen Wang, Gregory P. Way, Casey S. Greene, Joellen M. Schildkraut

Only recently has it become clear that epithelial ovarian cancer (EOC) is comprised of such distinct histotypes--with different cells of origin, morphology, molecular features, epidemiologic factors, clinical features, and survival patterns-that they can be thought of as different diseases sharing an anatomical location. Herein, we review opportunities and challenges in studying EOC heterogeneity. The 2014 World Health Organization diagnostic guidelines incorporate accumulated evidence that high- and low-grade serous tumors have different underlying pathogenesis, and that, on the basis of shared molecular features, most high grade tumors, including some previously classified as endometrioid, are now considered to be high-grade serous. At the same time, several studies have reported that high-grade serous EOC, which is the most common histotype, is itself made up of reproducible subtypes discernable by gene expression patterns. These major advances in understanding set the stage for a new era of research on EOC risk and clinical outcomes with the potential to reduce morbidity and mortality. We highlight the need for multidisciplinary studies with pathology review using the current guidelines, further molecular characterization of the histotypes and subtypes, inclusion of women of diverse racial/ethnic and socioeconomic backgrounds, and updated epidemiologic and clinical data relevant to current generations of women at risk of EOC.