title: Age-dependent morphological alterations of human ovaries from populations with and without BRCA mutations.
abstract: OBJECTIVE
  From analysis of pre-cancer ovarian tissues obtained from prophylactic oophorectomies, several studies reported the increased ovarian morphological changes in high-risk ovaries, but whether these morphological changes are associated with BRCA1/BRCA2 genotypes or are cancer precursors is controversial. Here, we have investigated a recent collection of ovaries from prophylactic oophorectomies and control ovaries from surgeries due to other non-ovarian-related cancer or non-neoplastic diseases to determine if ovarian morphological changes relate to BRCA1/2 genotypes or reproductive history.
  
  
  METHODS
  We assembled a panel of archived ovarian tissues: 52 ovarian tissue blocks were from prophylactic oophorectomies of a high-risk (HR) population; 66 ovaries were from surgeries due to non-ovarian-related diseases, referred to as normal-risk (NR) group. The morphology of ovarian tissues was examined, and morphological changes including papillomatosis, invaginations, inclusion cysts, and epithelial stratification were assessed in a blinded fashion.
  
  
  RESULTS
  No statistically significant difference in frequency of these histolopathologic features was found between HR and NR groups. However, inclusion cysts and deep invaginations were found much more commonly in women age 45-54 of either HR or NR groups.
  
  
  CONCLUSIONS
  This study suggests that no significant increase in the presence of non-neoplastic ovarian morphological changes is associated with BRCA1/BRCA2 mutations. Rather, the frequency of these histological features, especially inclusion cysts, may associate with age or menopausal status. We propose that ovulatory and perimenopausal gonadotropin stimulation produces ovarian morphological changes, and these histological features may promote the transformation of genetically compromised epithelial cells in the development of ovarian cancer.
authors.affiliation: Ovarian Cancer Program and Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, PA 19111, USA.
authors.forename: Kathy Qi
authors.initials: KQ
authors.lastname: Cai
authors.forename: Andres
authors.initials: A
authors.lastname: Klein-Szanto
authors.forename: Devarajan
authors.initials: D
authors.lastname: Karthik
authors.forename: Mitchell
authors.initials: M
authors.lastname: Edelson
authors.forename: Mary B
authors.initials: MB
authors.lastname: Daly
authors.forename: Robert F
authors.initials: RF
authors.lastname: Ozols
authors.forename: Henry T
authors.initials: HT
authors.lastname: Lynch
authors.forename: Andrew K
authors.initials: AK
authors.lastname: Godwin
authors.forename: Xiang-Xi
authors.initials: XX
authors.lastname: Xu
mesh_terms: D000367:Age Factors; D000368:Aged; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000473:pathology*; D010053:Ovary / Q000473:pathology*; D011230:Precancerous Conditions / Q000235:genetics* / Q000473:pathology*; D012307:Risk Factors