Ovarian surface epithelium as a source of ovarian cancers: unwarranted speculation or evidence-based hypothesis?

Abstract

Objectives: There has been increasing evidence that high grade serous ovarian carcinomas (HGSOCs), the most common and most lethal of all ovarian cancers, originate in oviductal fimbriae and metastasize to the ovary. The alternate hypothesis, that ovarian carcinomas may originate within the ovarian stroma in inclusion cysts lined by ovarian surface epithelium (OSE), has been criticized and often dismissed on the basis of the OSE's embryonic origin, mesothelial phenotype, tissue-specific markers, questionable ability to undergo metaplasia, and the lack of identifiable precursor lesions. This review analyzes these criticisms and summarizes evidence indicating that OSE as a source of ovarian cancers cannot be ruled out.

Methods: The literature was reviewed and representative reports were chosen to evaluate the current criticisms of, and evidence in favor of, the OSE hypothesis.

Results: The close developmental relationship between the oviduct and OSE, both of which originate in the mesothelial coelomic epithelium, accounts for their capacity to produce similar tumors. Histopathologic and experimental data show that OSE does undergo serous metaplasia, and that transformation of pure OSE cultures produces aggressive neoplasms resembling high- and low-grade serous carcinomas, but never mesotheliomas. There is evidence of premalignant changes (e.g. p53 inactivation) in morphologically normal OSE and of rare but definitive dysplastic and early preinvasive lesions in OSE-lined inclusion cysts. Conclusions based on tissue-specific markers to identify origins of inclusion cysts usually disregard the changes in differentiation occurring when OSE is displaced to the stroma. Lastly, an explanation is offered for the rare detection of precursor lesions in OSE-lined cysts, based on the likelihood that the duration from initiation of malignant transformation to invasive growth is minimal and thus difficult to detect.

Conclusion: The likelihood that HGSOCs originate both in fimbriae and in OSE should be considered in clinical decisions involving choices between prophylactic salpingo-oophorectomies and salpingectomies.