title: The fallopian tube as the origin of high grade serous ovarian cancer: review of a paradigm shift.
abstract: Research published over the past 10 years has suggested that most "ovarian cancer," and specifically the high-grade serous carcinoma (HGSC) subtype of ovarian cancer, actually originates in the fallopian tube. In this review, we examine the evidence supporting the tubal origin hypothesis for HGSC, and discuss the clinical implications of our improved understanding of the pathogenesis of ovarian cancer. We searched Medline R and Medline in-process and non-indexed citations from inception to December 15, 2012, to identify all English or French language articles discussing the origins of HGSC. Articles and findings were summarized descriptively. A step-wise transformation from normal epithelium to a lesion with the ability to invade and metastasize has been demonstrated within the fallopian tube. Intraepithelial or early invasive carcinoma of the fallopian tube is frequently identified in BRCA mutation carriers who undergo prophylactic risk-reducing salpingo-oophorectomy. In both BRCA mutation carriers and women from the general population, pre-invasive changes within the fimbriated end of the fallopian tube appear in association with early HGSC. Molecular and genetic studies, as well as in vitro and animal models, have also supported a tubal origin for HGSC. Whether the removal of fallopian tubes (salpingectomy) at the time of pelvic surgery for other reasons will lead to reductions in mortality from ovarian cancer is currently unknown, but it is an important area for future clinical research.
authors: Division of Gynaecologic Oncology, Princess Margaret Hospital, Department of Obstetrics and Gynaecology, University of Toronto, Toronto ON.
authors: Clare J
authors: CJ
authors: Reade
authors: Division of Gynaecologic Oncology, Princess Margaret Hospital, Department of Obstetrics and Gynaecology, University of Toronto, Toronto ON.
authors: Ruaidhrí M
authors: RM
authors: McVey
authors: Division of Gynaecologic Oncology, Princess Margaret Hospital, Department of Obstetrics and Gynaecology, University of Toronto, Toronto ON.
authors: Alicia A
authors: AA
authors: Tone
authors: Division of Gynaecologic Oncology, Department of Obstetrics and Gynaecology, University of British Columbia, Vancouver BC.
authors: Sarah J
authors: SJ
authors: Finlayson
authors: Division of Gynaecologic Oncology, Department of Obstetrics and Gynaecology, University of British Columbia, Vancouver BC.
authors: Jessica N
authors: JN
authors: McAlpine
authors: Division of Gynaecologic Oncology, The Ottawa Hospital-General Campus, Department of Obstetrics and Gynaecology, University of Ottawa, Ottawa ON.
authors: Michael
authors: M
authors: Fung-Kee-Fung
authors: Division of Gynaecologic Oncology, Princess Margaret Hospital, Department of Obstetrics and Gynaecology, University of Toronto, Toronto ON.
authors: Sarah E
authors: SE
authors: Ferguson
mesh_terms: D000818:Animals; D018284:Cystadenocarcinoma, Serous / Q000209:etiology* / Q000235:genetics / Q000473:pathology; D004848:Epithelium / Q000473:pathology; D005185:Fallopian Tube Neoplasms / Q000235:genetics / Q000473:pathology / Q000601:surgery; D005187:Fallopian Tubes / Q000473:pathology / Q000601:surgery; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D006801:Humans; D016239:MEDLINE; D009154:Mutation; D009361:Neoplasm Invasiveness; D010051:Ovarian Neoplasms / Q000209:etiology* / Q000235:genetics / Q000473:pathology; D010052:Ovariectomy; D058994:Salpingectomy
keywords: HGSC; high-grade serous carcinoma; ovarian cancer; salpingectomy; serous tubal intraepithelial carcinoma; tubal origin hypothesis