非小细胞肺癌表皮生长因子受体突变的检测与分子靶向治疗  

Detection of EGFR mutations in non small cell lung cancer and molecular targeted therapy

作　　者：方平 王沣 江富来 林琳 赵铁 

机构地区：[1]铜陵人民医院呼吸内科,铜陵244002

出　　处：《中华肺部疾病杂志（电子版）》2017年第5期543-548,共6页Chinese Journal of Lung Diseases(Electronic Edition)

基　　金：安徽省铜陵市卫生局科研基金[卫科研(2014)10]

摘　　要：目的探讨非小细胞肺癌患者表皮生长因子受体(EGFR)基因突变率和突变类型,分析其临床特征,并观察EGFR突变与表皮生长因子受体酪氨酸激酶抑制剂(EGFR-TKIs)治疗疗效的相关性。方法收集203例非小细胞肺癌患者外科手术、淋巴结活检、经皮肺穿刺活检、气管镜活检和胸腔积液沉渣石蜡标本,应用ADx-ARMS法进行EGFR基因突变检测,分析基因的突变率及其与临床特征的关系;观察非小细胞肺癌(NSCLC)接受EGFR-TKIs治疗的非小细胞肺癌患者的疗效。应用SPSS23.0软件进行统计学分析,计数资料比较采用χ2检验,采用Kaplan-Meier法计算患者的PFS,采用Log-Rank检验分析各种因素对生存期的影响。结果 203例NSCLC患者,男性116例,女性87例,年龄为25~82岁。吸烟指数≥400支/者61例,小于400支/年和不吸烟者142例,腺癌152例,鳞癌21例,腺鳞癌14例,其他NSCLC16例。203例NSCLC患者EGFR总突变率为51.2%(104/203),包括19外显子缺失突变51例(49.0%),21外显子L858R突变44例(42.3%),19del及L858R总突变率占所有突变的96.1%,18外显子G719X点突变3例(2.9%),19del+L858R双突变3例(2.9%),1例20ins,2例T790M突变分别为1例19del+T790M和1例L858R+T790M。EGFR基因阳性突变率女性组高于男性组(66.7%vs.36.2%);非吸烟组高于吸烟组(63.4%vs.16.4%);腺癌组高于鳞癌组(53.3%vs.33.3%),P<0.05。而EGFR基因突变状况与标本类型如手术、淋巴结活检、肺穿刺活检、气管镜活检和胸腔积液沉渣标本间无统计学差异,P=0.418。101例接受TKI治疗的NSCLC患者客观缓解率(ORR)为61.4%,疾病控制率(DCR)为71.3%,中位疾病无进展生存期(PFS)为10个月。其中EGFR突变阳性患者接受EGFR-TKIs治疗的ORR及DCR均要显著高于EGFR突变阴性及EGFR突变状态未明确人群(88.6%vs.16.7%vs.43.1%,P=0.000;95.5%vs.16.7%vs.56.9%,P=0.000)。EGFR突变阳性患者接受EGFR-TKIs治疗的中位PFS较EGFR突变阴性及EGFR突变状态未明确患者延长,有统计学差异(P=0Objective To detect epidermal growth factor receptor（ EGFR） mutations in non-small cell lung cancer（ NSCLC） patients,and to study the relationship between EGFR mutation and clinical features,pathological features,the therapy efficacy. Methods Collect 203 NSCLC patients,specimens,including surgical specimen,lymph node tissues,transthoracic needle biopsyspecimen,bronchoscopy biopsy specimen and pleural effusion cells specimen. EGFR mutations in 203 NSCLC were analyzed by ADx-AMRS assay. The relationship between the muta-tions and the clinicopathologic features was further evaluated. And observed the clinical efficacy of EGFR-TKIs. SPSS23. 0 software was used for statistical analysis,the data were compared with chi square test,PFS was calculated by Kaplan-Meier method,and the influence of various factors on survival was analyzed by Log-rank test. Results The age of 203 NSCLC patients,inluding 116 male and 87 female,was range 25 years to 82 years. Smoking index was greater than or equal to 400 in 61 cases,less than400 in 142 cases. The pathological characteristics of 203 cases were different,ininluding 152 cases of adenocarcinoma,21 cases of squamous cell carcinoma,14 cases of adenocarcinoma-squamous carcinoma,and other NSCLC 16 cases. The EGFR mutation rate of 203 cases in patients with NSCLC was 51.2%（ 104/203）,including 51 deletions in exon 19（ 49. 0%）,44 cases of exon 21 mutation,3 cases of exon 18 mutation（ 2.9%）,1 case of exon 20 mutation,3 exon 19/21 double mutation（ 2.9%）,1 case of 19del/T790 M and 1case of L858R/T790 M. The mutation rate of 19 del and L858 R were higher 96.1% in 104 cases. The mutation rates of EGFR were higher in females than those in males（ 66. 7% vs. 36. 2%）; Non smoking group EGFR mutation rate was higher than that in the smoking group（ 63.4% vs. 16.4%）; EGFR mutation rate of patients,with lung adenocarcinoma was higher than that of squamous cell carcinoma（ 53. 3% vs. 33. 3%）,P〈0. 05.Conversely,between EGFR gene mutation status and specimen type,incl

关 键 词：非小细胞肺癌 表皮生长因子受体 靶向治疗 

分 类 号：R563[医药卫生—呼吸系统]