多位点肺腺癌EGFR基因突变异质性及其对预后的影响  

Multi-points EGFR gene mutation heterogeneity in lung adenocarcinoma and its influence on the prognosis

作　　者：周文勇[1] 陈晓峰[1] 王邵华[1] 张慧君[2] 赵明川[3] 方玉超[1] 许东[1] 

机构地区：[1]同济医科大学附属上海肺科医院胸外科,200433 [2]同济医科大学附属上海肺科医院麻醉科,200433 [3]同济医科大学附属上海肺科医院肿瘤科200433

出　　处：《中华胸心血管外科杂志》2013年第10期604-609,共6页Chinese Journal of Thoracic and Cardiovascular Surgery

基　　金：吴阶平医学基金会资助（320.6740.10005）

摘　　要：目的探讨肺腺癌多位点EGFR基因突变及异质性存在状态及对患者整体预后的影响作用。方法回顾性分析2006年1月至2007年1月间76例Ⅲa期N2肺腺癌患者手术获取肺部原发灶组织及配对淋巴结转移灶组织标本。通过扩增阻滞突变系统（amplificationrefractorymutationsystem，ARMS）针对腺癌原发灶和配对淋巴转移灶EGFR基因突变检测，采用单因素分析和Cox比例风险模型多因素分析，分析EGFR基因突变及其异质性作为影响因子对预后的影响作用。结果全组检出EGFR基因突变40例（52．63％），其中9例（22．5％）表现为肺部原发灶与配对纵隔淋巴结转移灶间EGFR基因突变异质性。Log-Rank单因素检验结果，EGFR基因突变型与野生型患者术后总生存期对比差异无统计学意义（χ2=0．382，P=0．537），无疾病进展期对比具有显著性差异（χ2=4．147，P=0．042）；基因异质性因素对EGFR基因突变病例的总生存期和无疾病进展期不构成影响（矿=1．774，P=0．183；，=1．249，P=0．264）。Cox比例风险模型多因素检验提示，EGFR基因突变状态并非影响肺腺癌患者预后的独立风险因素。结论以往使用单一位点标本评估EGFR基因突变，不能够反应患者整体EGFR基因突变状态，可能造成靶向药物预测效果和实际使用效果间的偏差。在预测预后方面，EGFR基因状态作为独立影响因子对预后预测作用有限。Objective To do research on Multi-points EGFR gene mutation and heterogeneity in lung adenocarcinoma and its influence on the prognosis, to analyze EGFR gene mutation and its heterogeneity influence on patients＇overall prognosis. Methods The clinical features of patients with lung adenoearcinoma at stage llIa from January 2006 to January 2007 at our in- stitution were retrospectively reviewed. The primary lung tumors and corresponding metastatic lymph nodes tissue specimens were obtained by surgery. The adenoearcinoma primary nodes and corresponding metastatic lymph nodes EGFR mutation were detected by amplification refractory mutation system （ARMS）. Univariate analysis and multivariate analysis by Cox proportion- al-hazard model were used to analyze the impact of EGFR mutation and its heterogeneity as influential factor on patients ＂prog- nosis. Results 76 patients with the adenocarcinoma primary nodes and corresponding metastatic lymph nodes were detected by epidermal growth factor receptor （EGFR） mutation. 40 patients with EGFR mutation were detected （40/76, 52.63% ）. There were 9 specimens out of 40 who had lung primary nodes and corresponding metastatic lymph nodes EGFR gene heterogeneity （9/40,22.5%）. Log-Rank univariate analysis showed that there was no significant difference in overall survival period be- tween EGFR mutation patients and wild-type patients（χ2 = 0. 382, P = 0. 537 ）, but there was significant difference in illness- free progression period（χ2 =4. 147, P =0. 042）. Gene heterogeneity factor does not affect on the overall survival period and illness-free progression period of the patients with EGFR gene mutation （χ2 = 1. 774, P = 0. 183 ;χ2 = 1. 249, P = 0. 264）. Multivariate analysis by Cox proportional-hazard model showed that EGFR gene mutation is not the independent risk factor thathas赵 impact on the prognosis of patients with lung adenocarcinoma. Conclusion Assessment of EGFR gene mutations in a single-point specimen can not reflect the whole EGFR gen

关 键 词：腺瘤病  肺 EGFR基因突变 异质性 预后 

分 类 号：R734.2[医药卫生—肿瘤]