CAJ | 학술논문

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(amplification refractory mutation system,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(x2=0.382,P=0.537),无疾病进展期对比具有显著性差异(x2=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(x2=1.774,P=0.183 ;x2=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.
목적 탐토폐선암다위점EGFR기인돌변급이질성존재상태급대환자정체예후적영향작용.방법 회고성분석2006년1월지2007년1월간76례Ⅲa기N2폐선암환자수술획취폐부원발조조직급배대림파결전이조조직표본.통과확증조체돌변계통(amplification refractory mutation system,ARMS)침대선암원발조화배대림파전이조EGFR기인돌변검측,채용단인소분석화Cox비례풍험모형다인소분석,분석EGFR기인돌변급기이질성작위영향인자대예후적영향작용.결과 전조검출EGFR기인돌변40례(52.63％),기중9례(22.5％)표현위폐부원발조여배대종격림파결전이조간EGFR기인돌변이질성.Log-Rank단인소검험결과,EGFR기인돌변형여야생형환자술후총생존기대비차이무통계학의의(x2=0.382,P=0.537),무질병진전기대비구유현저성차이(x2=4.147,P=0.042)；기인이질성인소대EGFR기인돌변병례적총생존기화무질병진전기불구성영향(x2=1.774,P=0.183 ;x2=1.249,P=0.264).Cox비례풍험모형다인소검험제시,EGFR기인돌변상태병비영향폐선암환자예후적독립풍험인소.결론 이왕사용단일위점표본평고EGFR기인돌변,불능구반응환자정체EGFR기인돌변상태,가능조성파향약물예측효과화실제사용효과간적편차.재예측예후방면,EGFR기인상태작위독립영향인자대예후예측작용유한.
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 adenocarcinoma at stage Ⅲa from January 2006 to January 2007 at our institution were retrospectively reviewed.The primary lung tumors and corresponding metastatic lymph nodes tissue specimens were obtained by surgery.The adenocarcinoma primary nodes and corresponding metastatic lymph nodes EGFR mutation were detected by amplification refractory mutation system (ARMS).Univariate analysis and multivariate analysis by Cox proportional-hazard model were used to analyze the impact of EGFR mutation and its heterogeneity as influential factor on patients 'prognosis.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 between EGFR mutation patients and wild-type patients(x2 =0.382,P =0.537),but there was significant difference in illnessfree progression period(x2 =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 (x2 =1.774,P =0.183 ;x2 =1.249,P =0.264).Multivariate analysis by Cox proportional-hazard model showed that EGFR gene mutation is not the independent risk factor that has 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 gene mutation status,which may probably cause difference between targeted drugs'predicted effect and its actual usage effect.