Identifying BRAF mutations in colorectal cancer (CRC) by initial immunohistochemical (IHC) staining for mismatched protein expression as part of a Lynch syndrome screening program: A distinct clinicopathologic entity.

Abstract

405 Background: Multiple genetic mutations resulting in different clinical phenotypes have been found in colorectal adenocarcinoma. Mutation in the BRAF oncogene is a key step in malignant transformation within the methylator pathway leading to colorectal cancer. There is little data regarding the identification of the subset of CRCs exhibiting mutations in the BRAF oncogene with initial IHC staining, as well as a paucity of information describing this unique subset of colorectal cancers Methods: Between 1/1/11 to 12/31/12, all newly diagnosed CRCs underwent IHC testing for MLH1, MSH2, MHS6, and PMS2 protein expression if sufficient pathologic material existed. If MLH1 protein expression was absent, BRAF V600E mutation analysis was preformed. Patient demographics, pathology and outcomes were examined through chart review. Statistical associations were determined by the TTest, Fisher’s exact probability test and Cox regression analysis of Kaplan-Meier curves. Results: 314 newly diagnosed CRC patients were identified and 278 (89%) underwent IHC staining (study population). 48 had absent MLH1 protein expression (15%) and underwent BRAF mutational analysis. 35/48 had the V600E mutation. Comparing the BRAF mutated group to the study population without BRAF mutation showed statistically significant differences. These differences included median age at diagnosis (78 vs. 65 years, p < 0.0001), female sex (77% vs. 51%, p = 0.0037), right colon location (77% vs. 42%, p = 0.0001) and significant mucinous component denoted pathologically (31% vs. 7%, p = 0.0001). There was no difference in stage of CRC at diagnosis between the groups. Survival rates at one year based on Kaplan Meier curves were 65% vs. 82% and results will be updated. Conclusions: BRAF mutations in CRC are associated with unique clinicopathologic characteristics and overall worse prognosis. This subgroup of CRC can be identified as part of a Lynch Screening program via ICH staining of the mismatch repair proteins MLH1, MSH2, MSH6, and PMS2.