The Presence of Mucosal Iron in the Fallopian Tube Supports the “Incessant Menstruation Hypothesis” for Ovarian Carcinoma

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Abstract

The incessant ovulation hypothesis for the etiology of ovarian carcinoma has been accepted for decades, but recent evidence strongly implicates the fallopian tube mucosa as the source of most high-grade “ovarian serous carcinomas.” Menstrual reflux through the tubes, a normal phenomenon, is a putative source of tubal mucosal exposure to carcinogens. We searched for histologic evidence of deposition of iron, a well-recognized carcinogen, in the fallopian tubes in 196 women with advanced-stage high-grade pelvic serous carcinomas in comparison with 370 controls. Tubal hemosiderin and/or pseudoxanthoma cells were found in 20% of the serous carcinoma cases, and an iron stain was positive in 30% of a sample of pigment-negative cases. Controls displayed pigment in 5% (P<0.001). In both cases and controls, pigment was significantly more frequently present in women with endometriosis as compared with those without. We conclude that tubal mucosal iron is present in a significant proportion of women with advanced-stage high-grade pelvic serous carcinoma. As a carcinogen, iron may play a role in the pathogenesis of these tumors. As compared with the incessant ovulation hypothesis, the recently proposed “incessant menstruation hypothesis” may be a better explanation of the well-recognized association of ovarian carcinoma with the length of the reproductive life uninterrupted by pregnancy.

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