The pathogenesis and origin of ovarian cancer

Primary ovarian carcinoma is a heterogeneous group of diseases and each subtype is characterized by distinct clinical, histologic, and molecular features. Ovarian cancers can be broadly subdivided into Type I and Type II tumors. This classification is not a histologic one, but describes tumorigenic pathways based on clinically correlated molecular data. Type I tumors include low-grade serous, low-grade endometrioid, clear cell and mucinous carcinoma and typically present as a mass confined to the ovary and have a relatively good outcome. Type II tumors include high-grade serous carcinoma, high-grade endometrioid carcinoma, carcinosarcomas and undifferentiated carcinomas. These tumors are highly aggressive and typically present as advanced stage disease with poor outcomes. Two of the recent research spotlights in ovarian cancer field are: 1) elucidation of the origins of high-grade serous carcinoma, and 2) the revelation of genome-wide molecular landscapes of different histological subtypes of ovarian cancer. Mounting evidence has provided new evidence to argue that ovarian highgrade serous carcinoma may not originally develop from ovary. Rather, many of them are derived from fallopian tube epithelium then involve ovarian tissues secondarily. Similarly, it has been recognized that both ovarian clear cell carcinoma and endometrioid carcinoma develop from ovarian endometriomas which represent ectopic endometrial tissues. Accordingly, the only true primary ovarian neoplasms are gonadal stromal tumors and germ cell tumors, analogous to tumors in the testis. Recent efforts in comprehensive analysis of genomic changes have revealed the landscapes of many subtypes of ovarian cancer. It comes with no surprise that different types of ovarian cancer have unique landscapes that have profound implications on their pathogenesis and provide blue prints for future development of new strategies in early detection, prevention and targeted therapy. Both topics as outlined above will be discussed in the lecture and their highlights are briefly summarized in this abstract.