1. Pathology of ovarian cancers in BRCA1 and BRCA2 carriers
- Author
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Robert Winqvist, Jan G. M. Klijn, Lesley McGuffog, Barbara L. Weber, Paul D.P. Pharoah, Dominique Stoppa Lyonet, Hanne Meijers-Heijboer, D. Timothy Bishop, Heli Nevanlinna, Gilbert M. Lenoir, Dawn Steele, Hagay Sobol, Yves-Jean Bignon, Samantha Merrett, Laurent Arnout, Bruce A.J. Ponder, Douglas F. Easton, Fernando Schmitt, Sunil R. Lakhani, Franco Monti, Peter Devilee, Sanjiv Manek, Frédérique Penault-Llorca, Susan L. Neuhausen, Jocylyne Jacquemier, Adrienne M. Flanagan, Geoff Lane, Teresa Wagner, Ralf Bützow, Paolo Radice, Silvana Pilotti, Susanne Seitz, Ute Hamman, Medical Oncology, Clinical Genetics, and Human Genetics
- Subjects
Adult ,Cancer Research ,medicine.medical_specialty ,Pathology ,Heterozygote ,endocrine system diseases ,Receptor, ErbB-2 ,DNA Mutational Analysis ,Genes, BRCA1 ,Biology ,Immunophenotyping ,Cohort Studies ,03 medical and health sciences ,0302 clinical medicine ,Germline mutation ,SDG 3 - Good Health and Well-being ,Carcinoma ,medicine ,Odds Ratio ,Humans ,Genetic Predisposition to Disease ,skin and connective tissue diseases ,Pathological ,Germ-Line Mutation ,030304 developmental biology ,Genetic testing ,Aged ,Aged, 80 and over ,BRCA2 Protein ,Ovarian Neoplasms ,0303 health sciences ,medicine.diagnostic_test ,Anatomical pathology ,Odds ratio ,Middle Aged ,medicine.disease ,Prognosis ,Immunohistochemistry ,3. Good health ,Serous fluid ,Logistic Models ,Oncology ,030220 oncology & carcinogenesis ,Mutation ,Cancer research ,Disease Progression ,Female ,Tumor Suppressor Protein p53 ,Ovarian cancer - 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.
- Published
- 2004
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