212P - BRAF V600E: Prognostic Marker in Colorectal Cancer

Abstract

ABSTRACT Activation of BRAF oncogene has been implicated in colorectal carcinogenesis. BRAF protein is a serin/threonine kinase, component of a conserved signaling pathway that regulates cellular responses to exstracellular signals. In human cancer, it is commonly activated by somatic hotspot mutation at nucleotide 1799 of the BRAF gene which leads to a single aminoacid substitution Val600Glu (V600E). The aim of this study was to compare clinical and pathological phenotype of colorectal cancers with incidence of BRAF gene mutation. Clinical and pathological characteristics such as age, sex, tumor size, histologic grade, Dukes' stage, angioinvasion and tumor position were collected for each patient. Sections from 113 formalin-fixed paraffin-embedded (FFPE) tumor samples were evaluated for the BRAF V600E mutation using LightCycler PCR with allele-specific fluorescent probe melting curve analysis. Differences in clinical and pathological variables between the groups of patients with and without BRAF mutation were analyzed using Fisher exact test. Our results show that BRAF gene mutation was detected in 8.8% (10/113) samples. Statistical analysis revealed a significant association between the BRAF mutation and Dukes' stage (p = 0.04) where all mutations were found in tumors classified as Dukes'C (10/10). Incidence of mutation was higher in males, patients older than 60 years, tumors bigger than 5 cm, tumors with angioinvasion and poor differentiated tumors, but no significant association was found. All BRAF gene mutations were detected in colon cancers (p = 0.01). We can conclude that incidence of BRAF gene mutation was higher in tumors with poor prognostic markers which have been associated with poor tumor prognosis and progression of disease. Disclosure All authors have declared no conflicts of interest.