Support of the 'fallopian tube hypothesis' in a prospective series of risk-reducing salpingo-oophorectomy specimens

Eur J Cancer. 2013 Jan;49(1):132-41. doi: 10.1016/j.ejca.2012.07.021. Epub 2012 Aug 21.

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.

MeSH terms

  • Adult
  • Aged
  • Fallopian Tube Neoplasms / epidemiology*
  • Fallopian Tube Neoplasms / genetics
  • Fallopian Tube Neoplasms / prevention & control*
  • Female
  • Genes, BRCA1
  • Genes, BRCA2
  • Genetic Predisposition to Disease
  • Heterozygote
  • Humans
  • Middle Aged
  • Mutation
  • Neoplasms, Unknown Primary / epidemiology*
  • Neoplasms, Unknown Primary / genetics
  • Ovarian Neoplasms / epidemiology*
  • Ovarian Neoplasms / genetics
  • Ovarian Neoplasms / prevention & control*
  • Ovariectomy
  • Prevalence
  • Risk Factors