Immunohistochemical loss of BRCA1 protein in uterine serous carcinoma

Uterine serous carcinoma is a uncommon aggressive variant of endometrial cancer whose biologic origin is unclear. Mutations in p53 and BRCA1 genes play a key role in ovarian serous carcinogenesis. We investigated whether the loss of BRCA1 expression plays a similar role in uterine serous carcinoma. Loss of BRCA1 expression and Wilms tumor 1 (WT-1) overexpression were detected by immunohistochemical analysis. Depth of myometrial invasion, the presence of precursor lesions or polyps, and clinical parameters (age, history of breast cancer, and germline BRCA1 mutation status) were recorded. A total of 27 cases were available for evaluation. Three tumors (11.1%, 95% confidence interval, 2%-29%) showed the loss of BRCA1 expression. Two of these had known germline mutation in BRCA1, and the third had not been analyzed. Two of these cases expressed WT-1 or showed some morphologic features suggestive of drop metastasis from the adnexa, but no case showed detectable serous tubal intraepithelial carcinoma or features of an ovarian primary tumor. Overall, 5 women in the group had a personal history of breast cancer, and the finding was significantly associated with BRCA1 staining (P=0.049). A subset of uterine serous carcinomas shows the loss of BRCA1 protein and is associated with germline mutation.