The origin of ovarian cancers--hypotheses and controversies.

Ovarian cancer is the prime cause of death from gynecological malignancies in the Western world. In spite of its importance, it is poorly understood and its prognosis remains poor. The most common and lethal of all ovarian cancer subtypes are the high grade serous ovarian carcinomas (HGSOCs). A major problem in their clinical management is the current uncertainty about their cell type of origin, which limits means of early detection and prevention. It has not been resolved whether all HGSOCs originate in oviductal fimbriae or in ovarian surface epithelium (OSE). This review summarises evidence for these two hypotheses and considers the alternative possibility that HGSOCs may arise at both sites. This concept is based on the common embryonic origin of OSE and fimbriae in the coelomic epithelium and evidence of overlapping differentiation between these epithelia in the adult, which suggests incomplete commitment and pleuripotentiality. This hypothesis would account for OSE and fimbriae giving rise to identical carcinomas, and for their susceptibility to neoplastic transformation that is absent in the adjacent extraovarian serosa and oviductal ampulla.