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Clinicopathological and prognostic significances of EGFR , KRAS and BRAF mutations in biliary tract carcinomas in T aiwan
Author(s) -
Chang YuTing,
Chang MingChu,
Huang KaiWen,
Tung ChienChih,
Hsu Chiun,
Wong JauMin
Publication year - 2014
Publication title -
journal of gastroenterology and hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.214
H-Index - 130
eISSN - 1440-1746
pISSN - 0815-9319
DOI - 10.1111/jgh.12505
Subject(s) - kras , mutation , cancer research , medicine , epidermal growth factor receptor , stage (stratigraphy) , exon , biliary tract , gallbladder , egfr inhibitors , gene mutation , gene , oncology , cancer , colorectal cancer , biology , genetics , paleontology
Background and Aim Biliary tract carcinomas ( BTC s) are difficult to diagnose and treat. Epidermal growth factor receptor ( EGFR ) represents a therapeutic target for the BTC s. 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 BTC s resected at the N ational T aiwan U niversity H ospital between 1995 and 2004 were analyzed. The exons 18–21 of EGFR gene, the codon 12, 13 and 61 of KRAS gene, and BRAF V 600 E mutation were analyzed. We examined the correlation between these mutations and the overall survival, tumor location, stage, and differentiation in BTC s. 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 BTC s. BRAF mutation is rare in BTC s. EGFR mutation was an independent prognostic marker in BTC s 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 BTC s.