This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Schorge, J. O. Articles by Mok, S. C. Search for Related Content PubMed PubMed Citation Articles by Schorge, J. O. Articles by Mok, S. C.

BRCA1-related Papillary Serous Carcinoma of the Peritoneum Has a Unique Molecular Pathogenesis¹

Laboratory of Gynecologic Oncology [J. O. S., M. G. M., L. W. H., E. Z. K., R. S. B., S. C. M.] and Division of Women’s and Perinatal Pathology [W. R. W.], Brigham and Women’s Hospital; Division of Biostatistics, Dana-Farber Cancer Institute [S. J. L.]; and Department of Pathology, Massachusetts General Hospital [D.A.B.], Harvard Medical School, Boston, Massachusetts 02115

Papillary serous carcinoma of the peritoneum (PSCP) is believed to develop de novo from the peritoneal lining of the pelvis and abdomen. Although it is histologically indistinguishable from serous ovarian carcinoma, PSCP exhibits minimal or absent ovarian involvement and may even develop in a woman years after prophylactic oophorectomy. We have shown previously that patients with germ-line BRCA1 mutations who develop PSCP are more likely to have disease originating from multiple peritoneal sites compared with patients with wild-type BRCA1. In this study, we tested the hypothesis that BRCA1-related PSCP has a unique molecular pathogenesis. DNA was extracted from normal tissue and multiple tumor sites in patients with PSCP. BRCA1 and p53 gene mutations were screened for using single-strand conformation polymorphism. Loss of heterozygosity was determined at the BRCA1 and p53 loci. Immunohistochemical analyses of p53, epidermal growth factor receptor, erbB-2, erbB-3, erbB-4, and Bcl-2 expression were performed. We detected germ-line BRCA1 mutations in 11 (26%) of 43 PSCP patients. BRCA1 mutation carriers had a higher overall incidence of p53 mutations (89% versus 47%; P = 0.052), were more likely to exhibit multifocal or null p53 mutations (63% versus 7%; P = 0.014), and were less likely to exhibit erbB-2 overexpression (P = 0.013) than wild-type BRCA1 case subjects. We propose that the unique molecular pathogenesis of BRCA1-related PSCP may affect the ability of current methods to reliably prevent or detect this disease prior to metastasis.

This article has been cited by other articles:

				A. D. Levy, J. Arnaiz, J. C. Shaw, and L. H. Sobin From the Archives of the AFIP: Primary Peritoneal Tumors: Imaging Features with Pathologic Correlation RadioGraphics, March 1, 2008; 28(2): 583 - 607. [Abstract] [Full Text] [PDF]

				D. A. Levine, P. A. Argenta, C. J. Yee, D. S. Marshall, N. Olvera, F. Bogomolniy, J. A. Rahaman, M. E. Robson, K. Offit, R. R. Barakat, et al. Fallopian Tube and Primary Peritoneal Carcinomas Associated With BRCA Mutations J. Clin. Oncol., November 15, 2003; 21(22): 4222 - 4227. [Abstract] [Full Text] [PDF]

				R. E. Buller, T. A. Lallas, M. S. Shahin, A. K. Sood, M. Hatterman-Zogg, B. Anderson, J. I. Sorosky, and P. A. Kirby The p53 Mutational Spectrum Associated with BRCA1 Mutant Ovarian Cancer Clin. Cancer Res., April 1, 2001; 7(4): 831 - 838. [Abstract] [Full Text]