Revisiting the pathogenesis of ovarian cancer: the central role of the fallopian tube

Abstract

Among all gynecological malignancies, ovarian cancer is associated with the highest rate of mortality. Recent findings now propose a pivotal role for the fallopian tube during ovarian cancer pathogenesis. Until recently, ovarian cancer was thought to derive from the ovarian surface epithelium. Nevertheless, attempts to define a precursor lesion from this tissue failed. Instead, prophylactic surgery performed on BRCA mutation carriers and subsequent histological analyses revealed a characteristic pre-neoplastic alteration at the fimbriated end of the fallopian tubes, the so-called serous tubal intraepithelial carcinoma (STIC). By morphology and molecular genetics, STIC was found to resemble serous ovarian cancer. As STIC can also be detected in >60 % of BRCA-unrelated serous ovarian carcinomas, it is now considered to be the precursor of the most common ovarian cancer subtype. Based on this hypothesis, a salpingectomy, i.e., the removal of the post-reproductive fallopian tubes may remove the actual site of tumorigenesis and thereby prevent spreading over the ovarian surface and throughout the peritoneum. Consequently, prophylactic salpingectomy might protect against serous ovarian cancer. Moreover, the procedure interrupts the connection between the uterine cavity and the lesser pelvis. Hence, it prevents the ascension of exfoliated endometrial cells which will likely reduce the incidence of endometrioid and clear cell ovarian cancers. Increasing evidence suggests that serous ovarian cancer originates from the fimbriated distal end of the fallopian tube, whereas the ovary gets only involved at a later stage. Given the lack of suitable screening or early detection strategies for ovarian cancer, post-reproductive salpingectomy deserves serious consideration as a prophylactic intervention that will likely confer significant protection against an often deadly disease.