Department of Internal Medicine, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan.
J Gastroenterol Hepatol. 2014 May;29(5):1119-25. doi: 10.1111/jgh.12505.
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.
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.
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.
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.
胆道癌（BTC）难以诊断和治疗。表皮生长因子受体（EGFR）是 BTC 的治疗靶点。EGFR 基因的突变及其下游途径（包括 KRAS 和 BRAF）的激活预测了抗 EGFR 治疗的敏感性。本研究旨在分析 BTC 中的 EGFR、KRAS 和 BRAF 突变及其与临床结果的关系。
分析了 1995 年至 2004 年间在国立台湾大学医院切除的 137 例 BTC 石蜡包埋标本。分析了 EGFR 基因外显子 18-21、KRAS 基因密码子 12、13 和 61 以及 BRAF V600E 突变。我们检查了这些突变与 BTC 总生存率、肿瘤位置、分期和分化之间的相关性。
13 例（9.5%）BTC 患者存在 EGFR 突变，23 例（16.8%）患者存在 KRAS 突变。仅 1 例患者存在 BRAF 突变。单因素分析影响生存的因素是肿瘤分期、肿瘤分化和 EGFR 突变。多因素分析显示，EGFR 突变和肿瘤分期是独立的预后因素。未观察到 KRAS 或 BRAF 突变与预后相关。
EGFR 和 KRAS 突变在 BTC 中并不罕见。BTC 中 BRAF 突变罕见。除了肿瘤分期和分化外，EGFR 突变还是 BTC 的独立预后标志物。在肝外胆管癌和胆囊癌中未发现同时存在 EGFR 和 KRAS 突变。在为 BTC 患者制定分子靶向治疗方案时，应评估 EGFR 和 KRAS 突变情况。
