Is uterine serous papillary carcinoma a BRCA1-related disease? Case reportand review of the literature

Objectives. Type II endometrial carcinomas are estrogen-independent and hav e adverse histologic features and a substantially poorer prognosis. No risk factors have been identified. Interestingly, there is a striking clinical and histopathological similarity between serous papillary carcinomas of the ovary (OSPC), endometrium, and peritoneal cavity, suggesting a common onco genic mechanism. Several common molecular alterations were found using mole cular comparative analysis of OSPC and uterine serous papillary carcinoma ( USPC). Germline mutations in the BRCA1 tumor suppressor gene predispose to breast and ovarian cancer but no association with sporadic endometrial canc er has been found. A family of Ashkenazi Jewish origin, in which one sister was first diagnosed with USPC and the second diagnosed with OSPC, led to t he hypothesis that a BRCA mutation may contribute to USPC. Methods. Genomic DNA from both patients as well as two unaffected siblings was analyzed for the three mutations common in Ashkenazi Jews. Loss of hete rozygosity (LOH) analysis was performed on DNA extracted from USPC tumor ti ssue. Results. Both affected sisters tested positive for BRCA1 5382insC germline mutation. LOW analysis confirmed the results. Conclusions. We present a breast-ovarian cancer family including two sister s with advanced serous papillary carcinomas of endometrial and ovarian orig ins, carrying the same BRCA1 mutation (5382insC). LOW analysis on USPC tumo r DNA showed loss of the wild-type allele, suggesting a causal relationship between the germline BRCA1 mutation and USPC. We believe a study examining BRCA1 mutations in a large cohort of women with this high-risk endometrial carcinoma is warranted. A positive finding may have implications for surve illance and prophylactic surgery in carriers of BRCA1 mutations. (C) 1999 A cademic Press.