title: Pathology of ovarian cancers in BRCA1 and BRCA2 carriers.
abstract: OBJECTIVE
  Germline mutations in the BRCA1 and BRCA2 genes confer increased susceptibility to ovarian cancer. There is evidence that tumors in carriers may exhibit a distinct distribution of pathological features, but previous studies on the pathology of such tumors have been small. Our aim was to evaluate the morphologies and immunophenotypes in a large cohort of patients with familial ovarian cancer.
  
  
  METHODS
  We performed a systematic review of ovarian tumors from 178 BRCA1 mutation carriers, 29 BRCA2 mutation carriers, and 235 controls with a similar age distribution. Tumors were evaluated by four pathologists blinded to mutation status. Both morphological features and immunochemical staining for p53 and HER2 were evaluated.
  
  
  RESULTS
  Tumors in BRCA1 mutation carriers were more likely than tumors in age-matched controls to be invasive serous adenocarcinomas (odds ratio, 1.84; 95% confidence interval, 1.21-2.79) and unlikely to be borderline or mucinous tumors. Tumors in BRCA1 carriers were of higher grade (P < 0.0001), had a higher percentage solid component (P = 0.001), and were more likely to stain strongly for p53 (P = 0.018). The distribution of pathological features in BRCA2 carriers was similar to that in BRCA1 carriers.
  
  
  CONCLUSIONS
  Use of pathological features can substantially improve the targeting of predictive genetic testing. Results also suggest that BRCA1 and BRCA2 tumors are relatively aggressive and may be expected to have poor prognosis, although this may be treatment dependent.
authors.affiliation: The Breakthrough Toby Robins Breast Cancer Research Centre, Institute of Cancer Research, London, United Kingdom. Sunil.Lakhani@icr.ac.uk
authors.forename: Sunil R
authors.initials: SR
authors.lastname: Lakhani
authors.forename: Sanjiv
authors.initials: S
authors.lastname: Manek
authors.forename: Frederique
authors.initials: F
authors.lastname: Penault-Llorca
authors.forename: Adrienne
authors.initials: A
authors.lastname: Flanagan
authors.forename: Laurent
authors.initials: L
authors.lastname: Arnout
authors.forename: Samantha
authors.initials: S
authors.lastname: Merrett
authors.forename: Lesley
authors.initials: L
authors.lastname: McGuffog
authors.forename: Dawn
authors.initials: D
authors.lastname: Steele
authors.forename: Peter
authors.initials: P
authors.lastname: Devilee
authors.forename: Jan G M
authors.initials: JG
authors.lastname: Klijn
authors.forename: Hanne
authors.initials: H
authors.lastname: Meijers-Heijboer
authors.forename: Paolo
authors.initials: P
authors.lastname: Radice
authors.forename: Silvana
authors.initials: S
authors.lastname: Pilotti
authors.forename: Heli
authors.initials: H
authors.lastname: Nevanlinna
authors.forename: Ralf
authors.initials: R
authors.lastname: Butzow
authors.forename: Hagay
authors.initials: H
authors.lastname: Sobol
authors.forename: Jocylyne
authors.initials: J
authors.lastname: Jacquemier
authors.forename: Dominique Stoppa
authors.initials: DS
authors.lastname: Lyonet
authors.forename: Susan L
authors.initials: SL
authors.lastname: Neuhausen
authors.forename: Barbara
authors.initials: B
authors.lastname: Weber
authors.forename: Teresa
authors.initials: T
authors.lastname: Wagner
authors.forename: Robert
authors.initials: R
authors.lastname: Winqvist
authors.forename: Yves-Jean
authors.initials: YJ
authors.lastname: Bignon
authors.forename: Franco
authors.initials: F
authors.lastname: Monti
authors.forename: Fernando
authors.initials: F
authors.lastname: Schmitt
authors.forename: Gilbert
authors.initials: G
authors.lastname: Lenoir
authors.forename: Susanne
authors.initials: S
authors.lastname: Seitz
authors.forename: Ute
authors.initials: U
authors.lastname: Hamman
authors.forename: Paul
authors.initials: P
authors.lastname: Pharoah
authors.forename: Geoff
authors.initials: G
authors.lastname: Lane
authors.forename: Bruce
authors.initials: B
authors.lastname: Ponder
authors.forename: D Timothy
authors.initials: DT
authors.lastname: Bishop
authors.forename: Douglas F
authors.initials: DF
authors.lastname: Easton
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D024682:BRCA2 Protein / Q000235:genetics*; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D018450:Disease Progression; D005260:Female; D019398:Genes, BRCA1; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation; D006579:Heterozygote; D006801:Humans; D007150:Immunohistochemistry; D016130:Immunophenotyping; D016015:Logistic Models; D008875:Middle Aged; D009154:Mutation; D016017:Odds Ratio; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D024682:BRCA2 Protein; D018719:Erb-b2 Receptor Tyrosine Kinases; D016159:Tumor Suppressor Protein p53