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25-11-2016 | Ovarian cancer | Article

The disparate origins of ovarian cancers: pathogenesis and prevention strategies

Anthony N. Karnezis, Kathleen R. Cho, C. Blake Gilks, Celeste Leigh Pearce, David G. Huntsman


Ovarian cancer is the fifth cause of cancer-related death in women and comprises a histologically and genetically broad range of tumours, including those of epithelial, sex cord-stromal and germ cell origin. Recent evidence indicates that high-grade serous ovarian carcinoma, clear cell carcinoma and endometrioid carcinoma primarily arise from tissues that are not normally present in the ovary. These histogenetic pathways are informing risk-reduction strategies for the prevention of ovarian and ovary-associated cancers and have highlighted the importance of the seemingly unique ovarian microenvironment.

Nat Rev Cancer 2017; 17: 65–74. doi:10.1038/nrc.2016.113

Subject terms: Cancer genetics • Cancer stem cells • Endometrial cancer • Germ cell tumours • Gynaecological cancer • Ovarian cancer

Historically, one of the main reasons why the biology and evolution of common ovarian cancers have been so difficult to understand is because most tumour cells do not phenotypically resemble any normal cells in the ovary. For high-grade serous carcinoma (HGSC), the most common ovarian cancer, no credible histological precursor lesion had been identified until 15 years ago, and the majority of mucinous carcinomas of the ovary are metastases from other organs1. For other ovarian tumours, for which a precursor lesion has been identified, such as endometriosis for clear cell carcinoma (CCC) and endometrioid carcinoma (EC), it is still not known how the precursor develops2. These and other issues have substantially hampered our understanding of the origin of ovarian cancers and their pathogenesis, and thereby limited our ability to study them in experimental systems. Furthermore, the realization that the most common ovarian cancer types arise from cells that are not normally located in the ovary challenges the concept of what a 'true' ovarian cancer is.

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