OA: Of mice and women - Non-ovarian origins of “ovarian” cancer

Of mice and women - Non-ovarian origins of “ovarian” cancer

 

For many years, pathologists, clinicians, and researchers assumed that OCs arise from the ovarian surface epithelium (OSE) primarily because the dominant, and sometimes only, mass is found in the ovaries of women at presentation. The problem was compounded by the presence of widely disseminated disease at the time of diagnosis in many women with OC, particularly those with HGSC – obscuring potential “in situ” or precursor lesions. Many, if not most, HGSCs are now believed to arise from Müllerian epithelium, specifically the fallopian tube epithelium (FTE) on the tubal fimbriae, rather than the OSE [9] and [10]. The notion that HGSC often arises in the fallopian tube is strongly supported by the identification of occult tubal HGSCs and their presumptive precursors known as serous tubal intraepithelial carcinomas (STICs) in up to 12% of women with germline BRCA1/2 mutations who underwent risk-reducing bilateral salpingo-oophorectomy [11], [12], [13], [14], [15] and [16]. Importantly, in a study in which all resected fallopian tube tissue was examined from 41 women with tubo-ovarian or primary peritoneal HGSCs, tubal origin was presumed in nearly two-thirds based on the presence of tubal HGSC or STIC [17]. In three additional studies, STIC or invasive HGSC was confined to the tube in 22 of 29 cases in which tubo-ovarian HGSC was incidentally found in women without known or suspected genetic predisposition [18], [19] and [20]. Collectively, these reports provide strong evidence for tubal origin of sporadic HGSCs as well those arising in the high-risk context.

While supporting the conclusion that most HGSCs likely arise from tubal precursors, these studies raise some important questions.....