Pathology of Ovarian Cancers in BRCA1 and BRCA2 Carriers

Sunil R. Lakhani, Sanjiv Manek, Frederique Penault-Llorca, Adrienne Flanagan, Laurent Arnout, Samantha Merrett, Lesley McGuffog, Dawn Steele, Peter Devilee, Jan G M Klijn, Hanne Meijers-Heijboer, Paolo Radice, Silvana Pilotti, Heli Nevanlinna, Ralf Butzow, Hagay Sobol, Jocylyne Jacquemier, Dominique Stoppa Lyonet, Susan L. Neuhausen, Barbara WeberTeresa Wagner, Robert Winqvist, Yves Jean Bignon, Franco Monti, Fernando Schmitt, Gilbert Lenoir, Susanne Seitz, Ute Hamman, Paul Pharoah, Geoff Lane, Bruce Ponder, D. Timothy Bishop, Douglas F. Easton

Research output: Contribution to journalArticlepeer-review

Abstract

Purpose: 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. Experimental Design: 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.

Original languageEnglish
Pages (from-to)2473-2481
Number of pages9
JournalClinical Cancer Research
Volume10
Issue number7
DOIs
Publication statusPublished - Apr 1 2004

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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