Clinicopathological and prognostic significances of EGFR, KRAS and BRAF mutations in biliary tract carcinomas in Taiwan

• Published in: Journal of gastroenterology and hepatology Vol. 29; no. 5; pp. 1119 - 1125
• Main Authors: Chang, Yu-Ting, Chang, Ming-Chu, Huang, Kai-Wen, Tung, Chien-Chih, Hsu, Chiun, Wong, Jau-Min
• Format: Journal Article
• Language: English
• Published: Australia Blackwell Publishing Ltd 01.05.2014
• Subjects: Adult; Aged; Aged, 80 and over; biliary tract carcinomas; Biliary Tract Neoplasms - genetics; Biliary Tract Neoplasms - pathology; Biliary Tract Neoplasms - therapy; BRAF; Cell Transformation, Neoplastic - genetics; Codon - genetics; EGFR; Exons - genetics; Female; Humans; KRAS; Male; Middle Aged; Molecular Targeted Therapy; Mutation; Neoplasm Staging; Prognosis; Proto-Oncogene Proteins - genetics; Proto-Oncogene Proteins B-raf - genetics; Proto-Oncogene Proteins p21(ras); ras Proteins - genetics; Receptor, Epidermal Growth Factor - genetics; survival; Taiwan; biliary tract carcinomas; BRAF; KRAS; EGFR; survival
• ISSN: 0815-9319; 1440-1746; 1440-1746
• DOI: 10.1111/jgh.12505

Background and Aim Biliary tract carcinomas (BTCs) are difficult to diagnose and treat. Epidermal growth factor receptor (EGFR) represents a therapeutic target for the BTCs. Mutations of the EGFR gene and the activation of its downstream pathways, including KRAS and BRAF, predict the sensitivity to anti‐EGFR treatment. The aims of this study were to analyze the EGFR, KRAS and BRAF mutations in BTCs and their association with clinical outcomes. Methods Paraffin‐embedded specimens containing 137 BTCs resected at the National Taiwan University Hospital between 1995 and 2004 were analyzed. The exons 18–21 of EGFR gene, the codon 12, 13 and 61 of KRAS gene, and BRAF V600E mutation were analyzed. We examined the correlation between these mutations and the overall survival, tumor location, stage, and differentiation in BTCs. Results Thirteen (9.5%) BTC patients had EGFR mutations while 23 (16.8%) patients had KRAS mutations. Only one patient had BRAF mutation. Factors influencing survival on univariate analysis were tumor stage, tumor differentiation, and EGFR mutation. On multivariate analysis, EGFR mutation and tumor stage were independent prognostic factors. A correlation between KRAS or BRAF mutations and prognosis was not observed. Conclusions EGFR and KRAS mutations are not uncommon in BTCs. BRAF mutation is rare in BTCs. EGFR mutation was an independent prognostic marker in BTCs in addition to tumor stage and differentiation. No simultaneous EGFR and KRAS mutations in extrahepatic cholangiocarcinoma and gallbladder carcinoma were found. EGFR and KRAS mutations should be evaluated when tailoring molecular‐targeted therapy to patients with BTCs.