BRCA1-related papillary serous carcinoma of the peritoneum has a unique molecular pathogenesis

Papillary serous carcinoma of the peritoneum (PSCP) is believed to develop de novo from the peritoneal lining of the pelvis and abdomen. Although it I s histologically indistinguishable from serous ovarian carcinoma, PSCP exhi bits minimal or absent ovarian involvement and may even develop in a woman years after prophylactic oophorectomy, We have shown previously that patien ts with germ-line BRCA1 mutations who develop PSCP are more likely to have disease originating from multiple peritoneal sites compared with patients w ith wild-type BRCA1, In this study, we tested the hypothesis that BRCA1-rel ated PSCP has a unique molecular pathogenesis, DNA was extracted from norma l 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. Immunohis tochemical analyses of p53, epidermal growth factor receptor, erbB-2, erbB- 3, erbB-4, and Bcl-2 expression were performed. We detected germline BRCA1 mutations in 11 (26%) of 43 PSCP patients. BRCA1 mutation carriers had a hi gher overall incidence of p53 mutations (89% versus 47%; P = 0.052), were m ore 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) t han wild-type BRCA1 case subjects. We propose that the unique molecular pat hogenesis of BRCA1-related PSCP may affect the ability of current methods t o reliably prevent or detect this disease prior to metastasis.