非小细胞肺癌表皮生长因子受体基因突变与临床病理相关性研究

Epidermal growth factor receptor gene mutation and its clinicopathologic correlation with non-smal1 cell lung cancer

目的探讨中国人群非小细胞肺癌(NSCLC)表皮生长因子受体(EGFR)基因突变的临床病理学意义。方法采用荧光定量PCR法检测347例NSCLC患者癌组织中EGFR基因18、19、20、21号外显子突变状况,分析EGFR突变与临床病理学之间的关系。结果受检347例NSCLC样本中,检测出EGFR基因突变位点147个,发生在137例样本中(39.5%),其中18号外显子占总突变6.8%,19号外显子占40.1%,21号外显子占44.9%,20号外显子占8.2%,发现外显子存在同时突变的样本10例。其中女性患者突变率(56.5%)显著高于男性患者(25.9%),二者中差异极显著(P<0.01)。腺癌中变率为44.5%,鳞癌突变率为3%,低分化癌(非小细胞肺癌未分类)突变率为30.8%,腺鳞癌突变率为25%。腺癌EGFR突变率高于非腺癌(8/57),二者差异极显著(P<0.01)。年龄大小和取样不同与EGFR基因突变率无明显相关性。结论 NSCLC中EGFR基因突变常见于女性、腺癌,以第19号外显子缺失突变和第21号外显子点突变为主;利用荧光PCR法检测手术切除和穿刺活检样本突变率无明显差异,可有效用于EGFR基因突变检测。

Objective To investigate the clinicopathologic significance of the epidermal growth factor receptor （EGFR） gene mutation in Chinese patients with non-small cell lung carcinoma （NSCLC）. Methods Quantitative real-time PCR was used to detect EGFR gene mutation involving exons 18 -21 and then to analyze the correlation between the mutation and clinical pathological phenotype in 347 NSLCL patients. Results The overall mutation rate of EGFR gene in NSCLC was 39.5%. There were 10 cases of the mutations in exon 18 （6.8%） , 59 cases in exon 19 （40. 1% ） , 66 cases in exon 21 （44.9%） and 12 cases in exon 20 （8.2%）, among which two mutations existed simultaneously in 10 cases. The EGFR mutation rate in female patients （56.5%） was significantly higher than that of males （25.9%） （P 〈 0. 01 ）. The EGFR mutation rate in adenocarcinomas （44. 5% ） was much higher than that in squamous cell carcinomas （3%） ,poorly differentiated carcinomas （30. 8% ） and adenosquamous carcinomas （25%）. The mutation rate in adenocarcinomas was much higher than that in other cancer types（ 14% ） （P 〈 0.01 ）. The age （cutoff value： 60-year-old） and sample collection method （surgical samples and core biopsy sample） gave no statistical significance. Conclusions The EGFR mutations is commonly found in female and adenocarcinoma patients with NSCLC, especially in exons 19 and 21. Quantitative real-time PCR is a sensitive and accurate method to detect the EGFR gene mutations in either surgical or core biopsy samples.