title: Support of the 'fallopian tube hypothesis' in a prospective series of risk-reducing salpingo-oophorectomy specimens.
abstract: OBJECTIVE
  To determine the prevalence, localisation and type of occult (non)invasive cancer in risk-reducing salpingo-oophorectomy (RRSO) specimens in BRCA-mutation carriers and high-risk women from BRCA-negative families.
  
  
  METHODS
  A consecutive series of RRSO specimens of asymptomatic, screen-negative high-risk women were prospectively collected in our tertiary multidisciplinary cancer clinic from January 2000 until March 2012. All high-risk women in this study underwent genetic testing on BRCA-mutations. The surgico-pathological protocol comprised complete resection of ovaries and fallopian tubes, transverse sectioning at 2-3 mm (sectioning and extensively examining the fimbrial end [SEE-FIM] protocol from 2006) and double independent pathology review of morphologically deviant sections.
  
  
  RESULTS
  Three hundred and sixty RRSOs were performed in 188 BRCA1-carriers, 115 BRCA2-carriers and 57 BRCA-negative women at a median age of 44.0 years. Four occult invasive cancers were detected in BRCA-carriers (1.3%, 95%-confidence interval (CI) 0.03-2.61), all in BRCA1-carriers >40 years of age. All cancers, of which two tubal and two ovarian cancers, were FIGO-stage I/II. Three non-invasive serous intraepithelial carcinomas (STICs) were detected in BRCA-carriers (1.0%, 95%-CI 0.00-2.10). In BRCA-negative women one STIC was found (1.8%, 95%-CI 0.00-5.16), however she carried an unclassified variant in BRCA2. Total follow-up after RRSO was 1691 woman-years, in which one BRCA1-carrier developed peritoneal cancer (0.3%, 95%-CI 0.00-0.82).
  
  
  CONCLUSIONS
  A low prevalence of occult invasive cancer (1.1%) was found in young asymptomatic, screen-negative women at increased ovarian cancer risk undergoing RRSO. This study adds to the advice to perform RRSO in BRCA1-carriers before the age of 40. Our findings support the hypothesis of the fallopian tube as the primary site of origin of pelvic high-grade serous cancer.
authors.affiliation: Division of Gynecologic Oncology, Department of Obstetrics and Gynaecology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Welmoed
authors.initials: W
authors.lastname: Reitsma
authors.forename: Geertruida H
authors.initials: GH
authors.lastname: de Bock
authors.forename: Jan C
authors.initials: JC
authors.lastname: Oosterwijk
authors.forename: Joost
authors.initials: J
authors.lastname: Bart
authors.forename: Harry
authors.initials: H
authors.lastname: Hollema
authors.forename: Marian J E
authors.initials: MJ
authors.lastname: Mourits
mesh_terms: D000328:Adult; D000368:Aged; D005185:Fallopian Tube Neoplasms / Q000453:epidemiology* / Q000235:genetics / Q000517:prevention & control*; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D009382:Neoplasms, Unknown Primary / Q000453:epidemiology* / Q000235:genetics; D010051:Ovarian Neoplasms / Q000453:epidemiology* / Q000235:genetics / Q000517:prevention & control*; D010052:Ovariectomy; D015995:Prevalence; D012307:Risk Factors