The Molecular Fingerprint of High Grade Serous Ovarian Cancer Reflects Its Fallopian Tube Origin

Abstract

High grade serous ovarian cancer (HGSC), the most lethal and frequent type of epithelial ovarian cancer (EOC), has poor long term prognosis due to a combination of factors: late detection, great metastatic potential and the capacity to develop resistance to available therapeutic drugs. Furthermore, there has been considerable controversy concerning the etiology of this malignancy. New studies, both clinical and molecular, strongly suggest that HGSC originates not from the surface of the ovary, but from the epithelial layer of the neighboring fallopian tube fimbriae. In this paper we summarize data supporting the central role of fallopian tube epithelium in the development of HGSC. Specifically, we address cellular pathways and regulatory mechanisms which are modulated in the process of transformation, but also genetic changes which accumulate during disease progression. Similarities between fallopian tube mucosa and the malignant tissue of HGSC warrant a closer analysis of homeostatic mechanisms in healthy epithelium in order to elucidate key steps in disease development. Finally, we highlight the importance of the cancer stem cell (CSC) identification and understanding of its niche regulation for improvement of therapeutic strategies.

Distribution and case-fatality ratios by cell-type for ovarian carcinomas: A 22-year series of 562 patients with uniform current histological classification

“…The best evidence for this is from women with germline BRCA mutations. These advances have been supported by numerous morphological and molecular biological studies and studies in animal models [1][2][3][4][5][6][7][8]. It is essential for all types of biological studies of cancer to have a firm foundation in histopathology to provide the requisite context.…”

Serous Tubal Intraepithelial Carcinoma Localizes to the Tubal-peritoneal Junction

“…The fallopian tube as the site of origin of ''ovarian cancer'' was proposed by Dutch investigators (18) after several studies of prophylactic salpingo-oophorectomy specimens from high-risk women revealed small tubal carcinomas (1,16). There is now a stream of reports worldwide that confirm and expand on these data with morphologic and molecular studies as well as observations in animal models (19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34).…”

Differential Transcriptional and Protein Expression of Thyroid-Stimulating Hormone Receptor in Ovarian Carcinomas

“…1 The pathogenesis of epithelial ovarian cancer represents a field of intense research, especially after the recognition that differences in histology may reflect differences in tumor development. 2 Furthermore, potential risk factors, such as endometriosis, 3 ovarian cysts, 3 and certain genetic deficiencies have been identified, 2 whereas thyroid disease has been recently linked epidemiologically to the development of ovarian cancer. 3 In addition, it is known that ovarian cyst formation may be more frequent in women with primary hypothyroidism 4 and in experimentally hypothyroid animals exposed to stimulation with gonadotropins.…”