The origin of serous ovarian cancer may be found in the uterus: a novel hypothesis

Since 1971 the incessant ovulation theory by Fathalla is widely accepted as theory for ovarian carcinogenesis, supported mainly by epidemiological findings. However, this theory cannot explain the protective effect of hysterectomy and tubal ligation on the incidence of ovarian cancer. Furthermore, never a precursor lesion has been identified in the ovary itself. Although recently the fallopian tube has been proposed as possible site of origin, there are reasons to believe that a precursor lesion for ovarian and pelvic serous carcinoma is located within the uterus. Uterine serous papillary carcinoma (UPSC) resembles serous ovarian and pelvic carcinoma in behavior and prognosis. Its precursor lesion endometrial intraepithelial carcinoma (EIC) is non-invasive and often multifocal in origin. Importantly, these premalignant cells have a loosely cohesive nature and are able to spread to intraperitoneal surfaces easily, thereby often found on the surface of ovaries or in the fallopian tube. We hypothesize that EIC is a precursor lesion of serous ovarian carcinoma, originating in the uterus and spreading into the intraperitoneal cavity via a mechanism as is accepted for endometriosis. To illustrate this, some cases of serous ovarian carcinoma with concordant EIC in the endometrium as only precursor lesions are presented. A paradigm shift with respect to the origin of ovarian cancer from the ovary to the endometrium could have enormous consequences for primary and secondary preventive strategies to decrease the mortality from this disease.