B-RAF V600E Mutations in Endometrial Adenocarcinoma
Steven Hang, Virgina Breese, Mai He, Cunxian Zhang, JinJun Xiong, Cynthia L Jackson. Warren Alpert Medical School of Brown University, Providence, RI; Rhode Island Hospital, Providence, RI; Women & Infants Hospital of Rhode Island, Providence, RI
Background: The EGFR-KRAS-BRAF pathway plays a critical role in the development of many types of malignancies including lung, colon and ovarian cancers. Previous studies have only reported the detection of B-RAF mutations other than the V600E mutation in endometrial adenocarcinoma. Our current study aims to investigate the prevalence of B-RAF V600E mutations in endometrial adenocarcinoma in our patient population.
Design: With IRB approval, nineteen (19) endometrial adenocarcinoma cases were selected for this study. Genomic DNA was extracted from formalin-fixed paraffin-embedded tissue sections that were microdissected to ensure more than 80% tumor cells. B-RAF V600E mutations were first screened using mutant allele-specific real-time PCR. Positive cases were then verified by direct sequencing using capillary electrophoresis. B-RAF V600E mutation results were also compared to the K-RAS results obtained from our previously reported study.
Results: B-RAF V600E mutations were detected in 3 of 19 (15.8%) endometrial adenocarcinomas, significantly higher than what has been reported in the literature (P<0.02, Fisher's Exact Test, compared to 0/44, Kawaguichi M et al., 2009). Two of the cases positive for B-RAF V600E mutations were endometrioid adenocarcinoma while the third was endometrioid adenocarcinoma with significant mucinous differentiation. These three positive cases did not harbor KRAS mutations.
Conclusions: Unlike previous reports in endometrial adenocarcinoma, B-RAF V600E mutations were found in our patient group using two different technical approaches. These results, compared to our previous K-RAS study (Mod Pathol 2011;24 Supp 1 :270A), indicate that B-RAF V600E mutations contribute to the tumorigenesis of endometrial carcinoma at a lower frequency than K-RAS mutation. Further investigation of B-RAF V600E mutation in sub-types of endometrial adenocarcinoma and its prognostic significance is strongly warranted.
Category: Gynecologic & Obstetrics
Wednesday, March 21, 2012 9:30 AM
Poster Session V # 145, Wednesday Morning