Abstract 2129A: Clinical implications of infrequent BRAF mutation in advanced stage low-grade ovarian serous carcinomas

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Abstract Serous carcinoma is the most common histologic subtype of epithelial ovarian cancer. Recent evidence strongly suggests that a 2-tier system stratifying serous carcinoma into low-grade and high-grade categories is biologically and clinically relevant. Low-grade ovarian serous carcinomas are believed to arise via an adenoma-borderline-carcinoma sequence. We analyzed 91 ovarian tumor samples for mutations in BRAF, KRAS, and TP53. No TP53 mutations were detected in serous borderline tumors (n = 30) or low-grade serous carcinomas (n = 43), but 73% of high-grade serous carcinomas (n = 18) carried a TP53 mutation. BRAF and KRAS mutations together were detected in 47% of serous borderline tumors, but among the low-grade serous carcinomas, only 2% had a BRAF mutation and 19% had a KRAS mutation. The low frequency of BRAF mutations in advanced stage low-grade serous carcinomas suggests that low-grade serous carcinomas are likely derived from serous borderline tumors without BRAF mutations. This hypothesis is further supported by the fact that 2 of the patients with serous borderline tumors without BRAF or KRAS mutations developed recurrent low-grade serous carcinoma 17 and 60 months after the initial diagnosis of a serous borderline tumor. Moreover, it is interesting that 4 of the 8 patients with either BRAF or KRAS mutations have had no evidence of disease after optimal debulking surgery and standard platinum-taxane-based chemotherapy, while patients without mutations are either diseased or alive with recurrent disease. Thus, mutational analysis of BRAF may have prognostic utility in that a finding of a BRAF mutation may suggest a low risk of recurrent low-grade serous carcinoma. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2129A.