原发SCLC中EGFR突变异质性及其预后关系

目的 在大规模中国人群SCLC标本中检测EGFR基因突变频率,分析原发SCLC中EGFR基因突变的异质性和临床特征。方法 2009—2014年间共收集557例单纯SCLC患者组织样本。利用双脱氧测序法进行EGFR突变检测。χ²检验分析临床因素与EGFR突变的相关性,Kaplan-Meier法进行生存分析,Cox模型多因素预后分析。结果 在557例标本中检测到38例EGFR突变(6.8%),其中经典突变有E19 deletion的3例、 E21 L858R的3例、E20 T790M突变的1例,余均为非经典突变。EGFR突变与患者性别、年龄、临床分期无相关性。不吸烟者与吸烟患者之比在EGFR突变组(11/36)与EGFR野生组(86/398)差异无统计学意义(P=0.080)。对患者治疗史进行匹配发现EGFR突变者生存预后比EGFR野生型好,中位生存期分别为(24.43±9.46)个月∶(14.17±0.84)个月(P=0.020)。采用Cox回归分析提示局限期(HR=2.610,P=0.000)、<65岁(HR=1.476,P=0.010)和EGFR突变是预后影响因素(HR=0.576,P=0.039)。结论 在初诊SCLC患者中存在EGFR突变亚群,其突变类型异质性较高,EGFR突变与SCLC患者的生存呈正相关。

Epidermal growth factor receptor mutations in primary small cell lung cancer:genetic heterogeneity and prognostic impacts

Objective To conduct a large-scale survey of the epidermal growth factor receptor (EGFR) mutations among Chinese small cell lung cancer (SCLC) patients, and to analyze the genetic heterogeneity and clinical characteristics of EGFR mutations in primary SCLC. Methods From 2009 to 2014, tissue specimens were collected from a total of 557 patients with SCLC.A total of 45 surgery and 512 biopsy samples are included. Dideoxy sequencing was used to determine the EGFR mutations. The chi-square test was used to analyze the correlation between clinical variables and EGFR mutations. Survival analysis was performed using the Kaplan-Meier method. Multivariate prognostic analysis was made by the Cox model. Results In the 557 specimens, 38 had EGFR mutations (6.8%), containing 3 with E19 deletion, 3 with E21 L858R, 1 with E20 T790M, and others with non-classical mutations. There was no correlation of EGFR mutations with gender, age, or clinical stage. There was no significant difference in proportion of non-smokers between patients with and without EGFR mutations (11/36 vs. 86/398, P=0.080). After the patient-treatment history matching, patients with EGFR mutations had a significantly longer median overall survival time than those without EGFR mutations (24.43±9.46 vs. 14.17±0.84 months, P=0.020), indicating a better prognosis in patients with EGFR mutations. The Cox regression analysis suggested that limited stage disease, age of<65 years, and EGFR mutations were prognostic predictors (HR=2.610, 1.476,0.576, P=0.000,0.010,0.039). Conclusions EGFR mutations with high genetic heterogeneity can be found among the patients newly diagnosed with SCLC. EGFR mutations are positively correlated with the survival of patients with SCLC.