非小细胞肺癌组织表皮生长因子受体基因突变的临床意义

目的探讨非小细胞肺癌(NSCLC)肿瘤组织表皮生长因子受体(EGFR)基因突变及其相关因素.方法抽取80例手术切除肿瘤组织DNA,采用巢式PCR方法对编码EGFR基因的第18、19和21外显子片段进行扩增和测序,用Chromas软件分析基因突变或缺失.结果21例肿瘤组织存在EGFR基因突变或缺失,发生率为26.25%,其中13例为EGFR第19外显子阅读框内多核苷酸的缺失,8例为第21外显子2 573位核苷酸点突变.这些突变均为杂合子型.肺腺癌突变率为42.10%(16/38),显著高于鳞癌的9.68%(3/31)和鳞腺混合癌的18.2%(2/11)(χ2=9.702,P ＜0.01);女性患者突变率为48.28%(14/29),显著高于男性患者的13.73%(7/51)(χ2=11.4,P＜0.01);不吸烟者突变率为40%(16/40),显著高于吸烟者的12.50%(5/40)(χ2=7.812,P＜0.01).EGFR基因突变与患者年龄、TNM分期等因素无关.Logistic回归分析提示患者性别和组织类型是影响EGFR突变的2个主要因素.结论NSCLC存在EGFR基因的突变或缺失,其中以女性、腺癌和不吸烟患者突变率较高.

Epidermal growth factor receptor mutations in Chinese patients with non-small cell lung cancer

Objective To investigate mutations of EGFR TK gene in the tumors of Chinese NSCLC patients and analyze factors related with the mutations. Methods EGFR tyrosine kinase genes (exons 18,19 and 21) were sequenced in 80 NSCLC patients. The incidence of the mutations of EGFR gene was compared among sexes, smoking status, histology etc. Results Somatic mutations were identified in the tyrosine kinase domain of the EGFR gene in 21 of 80 NSCLC patients with the incidence of 26. 25 %. In-frame deletions of exon 19 occurred in 13 patients and point mutation occurred in codon 858(exon 21) in 8 patients. All mutations were heterozygous and identical mutaions were observed in multiple patients. The mutations were significantly higher in the adenocarcinoma than in squamous carcinoma and squamous-adenocarcinoma (16/38vs 3/31 vs 2/11, X2 =9. 702, P<0.01). in the female patients than in the male patients (14/29 vs7/51 ,X2 = 11. 4, P <0. 01)and in non-smokers than in smokers (16/40 vs 5/40, X2 = 7. 812, P <0. 01). The mutations were not related to patients' age, TNM staging, etc. Logistic multi-factor regression analysis showed that the mutations were highly associated with genders and tumor histology of the patients. Conclusion Somatic mutations of EGFR gene develop in NSCLC and are more common in the female, non-smoker and adenocarcinoma patients.