非小细胞肺癌组织EGFR突变及其临床意义的研究

目的:检测非小细胞肺癌(NSCLC)患者表皮生长因子受体(EGFR)的突变,探讨突变特征及其在肺癌治疗中的意义。方法:收集46例手术切除肺癌组织及其癌旁组织,分别提取DNA,采用PCR法扩增编码EGFR基因的第18、19、20及21外显子片段,对扩增片段进行DNA测序及分析。结果:46例NSCLC中12例(26.1%)患者肺癌组织存在EGFR酪氨酸激酶结合域的体细胞突变;癌旁组织均未发现突变。12例突变中,9例(75.0%)19号外显子上发生缺失突变,3例(25.0%)21号外显子上发生替代突变。伴细支气管肺泡癌分化特征的肺腺癌突变率(7/9,77.8%)显著高于普通腺癌(5/23,21.7%)和鳞癌(0/12,0)的突变率,P<0.05;女性突变率(9/15,60%)显著高于男性(3/31,9.7%),P<0.05;不吸烟者突变率(9/20,45%)显著高于吸烟者(3/26,11.5%),差异均有统计学意义,P<0.05。结论:国内NSCLC患者存在EGFR突变,女性、非吸烟者及伴细支气管肺泡癌分化特征的肺腺癌提示突变的高发性。

Clinical significance of EGFR mutation in NSCLC tissnes

OBJECTIVE:To detect the mutation of epidermal growth factor receptor(EGFR) in patients with non-small cell lung cancer(NSCLC),and investigate the characteristics of EGFR mutation and its clinical significance for NSCLC.METHODS:Specimens of lung cancer tissues and corresponding paracarcinoma tissues were collected from 46 NSCLC patients.DNA was extracted from the 46 specimens respectively.Exon18,19,20 and 21 EGFR genes were amplified by PCR to be sequenced.RESULTS:Somatic mutation in tyrosine kinase(TK) domain of EGFR in 12 of 46 NSCLC patients(26.1%) was identified in carcinoma tissues.Mutation was not found in corresponding paracarcinoma tissues.In 12 mutation cases,9 cases(75.0%) were in-frame deletion in exon 19 and 3 cases(25.0%)were amino acid substitution in exon 21.The mutation rate was significantly higher in adenocarcinoma with bronchioloalveolar carcinoma(BAC) component(7/9,77.8%) than pure adenocarcinoma(5/23,21.7%),P<0.05;significantly higher in women(9/15,60%) than men(3/31,9.7%),P<0.05;significantly higher in non-smokers(9/20,45%) than smokers(3/26,11.5%),P<0.05.CONCLUSIONS:Somatic mutation of EGFR gene exist in NSCLC patients.Female,non-smoker and adenocarcinoma with any degree of BAC predicte the high presence of EGFR mutation.