Abstract 2429: Increased incidence of brain metastases in BRCA1 related ovarian cancers

Abstract

Abstract Objective: Brain metastasis to ovarian cancer is a very rare phenomenon. BRCA1 related ovarian cancers show specific pathobiological profiles, an advanced stage, and sensitivity to chemotherapeutic agents. However, no clear relationship to any known metastatic behavior has yet been found, so we examined the BRCA1 mutation and expression profiles in ovarian cancer cases with brain metastases. Methods: We examined our clinical records of 320 ovarian cancer cases from 1983 to 2008 in order to ascertain cases with brain metastases. In the molecular genetic analyses, we performed loss of heterozygosity (LOH), direct sequence, and immunohistochemical staining analysis of BRCA1. For LOH analysis, 4 markers spanning the region of BRCA1 were selected for use. The entire exons, 23 exons in BRCA1 and 26 exons in BRCA2, and the intronic boundary regions were sequenced in both forward and reverse directions for detecting germline mutations. The immunohistochemical studies were performed with the BRCA1 C-terminal mouse monoclonal antibody (Ab-3, Calbiochem,×500) Results: We ascertained 7 cases with brain metastases in 320 ovarian cancer cases (7/320=2.2%). Among the 7 cases, 3 cases had ovarian and/or breast cancer patients in third-degree relatives. We detected 4 LOH-positive cases and a germline mutation of BRCA1 in 2 of the 4 cases, Q934X and L63X respectively. Furthermore, the remaining 2 cases showed an absent staining of the BRCA1 protein. Therefore, 4 out of 7 cases with brain metastases were considered BRCA1-related ovarian cancers (4/7=57.1%). All 4 of the cases were serous adenocarcinoma of ovary. Conclusions: This is the first report of a hospital population-based study in relation to brain metastasis and BRCA1-related ovarian cancers. Our results suggest that the loss of BRCA1 function may be involved in the phenomenon of brain metastasis to ovarian cancer. Further molecular biologic analyses will be required for a better understanding of this rare phenomenon. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2429. doi:10.1158/1538-7445.AM2011-2429