Overview of Epithelial Ovarian Carcinoma (EOC): Pathogenesis and General Considerations

Abstract

Epithelial ovarian carcinomas (EOCs) comprise a heterogeneous group of neoplasms, the five most common subtypes being high-grade serous, low-grade serous, endometrioid, clear cell, and mucinous. In recent years, our understanding of the underlying pathogenesis and initiating molecular events in the different tumor subtypes has greatly increased, and although EOC is often considered clinically as one disease, there is now an increasing realization that the various subtypes have a different natural behavior and prognosis. Although at present, adjuvant therapy is mainly dependent upon tumor stage and grade rather than cell type, this is likely to change in the future with the development of new chemotherapeutic agents and targeted therapies against specific tumor subtypes or even specific molecular abnormalities. It is now firmly established that there are two distinct types of ovarian serous carcinoma, low grade and high grade, the former being much less common and arising in many cases from a serous borderline tumor. Low-grade and high-grade serous carcinomas represent two distinct tumor types with a different underlying pathogenesis rather than low-grade and high-grade variants of the same neoplasm. There is now emerging and compelling evidence that many high-grade serous carcinomas (by far the most common subtype of EOC) actually arise from the epithelium of the distal fallopian tube. Primary ovarian mucinous carcinomas are relatively uncommon, mostly unilateral and stage I, and largely of so-called intestinal or enteric type. Most arise in a stepwise manner from a preexisting mucinous cystadenoma and mucinous borderline tumor. Endometrioid and clear cell carcinomas typically present as low-stage neoplasms and in many, or most, cases arise from endometriosis; the former are usually well differentiated, and there is now evidence that the majority of neoplasms reported in the past as high-grade endometrioid carcinoma are of serous type. WT1 is useful in this regard since it is a relatively specific marker of a serous phenotype. It is recommended that different subtypes of EOC are graded using different systems rather than employing a universal grading system. Since most serous carcinomas are likely to arise from the fallopian tube and endometrioid and clear cell carcinomas mostly evolve from endometriosis which, via a process of retrograde menstruation, is ultimately of endometrial origin in most cases, it can be considered that true primary EOCs are rare, analogous to the situation in the testis.