open access: The origin of ovarian cancer (including references to familial/non-familial ovarian cancer/inclusion cysts...)

"According to Hamilton,¹ the concept that epithelial ovarian cancers arise from ovarian surface epithelial (OSE) cells was proposed by Sir Spencer Wells in 1872. More than a century later, this hypothesis remains controversial....Over the last decade several fundamental observations have documented that epithelial ovarian cancers should no longer be considered as a single disease entity."

Conclusion and future directions

There is recent compelling evidence that histological subtypes of epithelial ovarian cancers represent different disease entities that are characterised by distinct molecular changes. Research into the biology of those cancers, including an investigation of their cell of origin, should therefore be subtype-specific.

The finding by Sharma et al. does not refute the hypothesis of the ovarian origin of epithelial ovarian cancer, but does provoke a discussion about the cellular origin of these cancers. The fallopian tube epithelium is very likely to play an important role in the development of HGSOCs in women with BRCA mutations, and in a subset of non-familial HGSOCs. This does not, however, explain the origin of the majority of sporadic ovarian cancers that may grow directly from the ovary without tubal involvement. It is interesting to note that the data from Sharma et al. show a trend towards an increased risk of epithelial ovarian cancer in women with ICs (inclusion cysts) (relative risk of 1.92), albeit a statistically non-significant increase in risk. It is possible that much smaller ICs may have been missed by pelvic ultrasound, and that those could have contributed to the development of a fraction of epithelial ovarian cancers in the IC-negative women. The evolving model of a tubal origin of ovarian cancer, however, has important implications for future clinical and research directions.

The role of prophylactic salpingectomy alone in reducing the risk of epithelial ovarian cancer should be evaluated only in prospective clinical studies. Novel imaging modalities for the detection of early tubal lesions are needed to investigate the value of early detection of tubal intraepithelial carcinomas in reducing the risk of development of invasive epithelial ovarian cancer.
It is also crucial that further characterisation of the molecular events that control orderly cell division and differentiation of tubal epithelium should be investigated to gain insights into the initiation and progression of pelvic serous cancers.