非小细胞肺癌290例表皮生长因子受体基因突变和拷贝数的检测分析

Status of gene mutation and copy number of EGFR in 290 cases of non-small cell lung carcinoma

目的检测非小细胞肺癌（NSCLC）组织中表皮生长因子受体（EGFR）基因突变和拷贝数，明确中国NSCLC人群中EGFR基因状态。方法应用显微切割技术和蝎形探针扩增阻滞突变系统（Scorpions ARMS）联合检测290例石蜡包埋、甲醛固定的NSCLC组织中其EGFR基因突变状态，并应用荧光原位杂交（FISH）技术检测其中209例EGFR基因拷贝数的情况，分析EGFR基因突变和EGFR基因拷贝数二者之间的关系，探讨EGFR基因状态与肺癌临床病理特点的相关性。结果NSCLC组织EGFR突变率为41．7％（121／290），其中腺癌为48．4％，大细胞癌为16．7％，鳞癌为0。EGFR基因突变以第19、21外显子突变为主（92／121），其中6例存在两种类型的突变。EGFR基因FISH阳性率为51．2％（107／209），包括29例扩增，78例高多体性。其中腺癌FISH阳性率为52．1％，大细胞癌为75．0％，鳞癌为11．1％。检测结果显示NSCLC组织EGFR基因突变与EGFR基因高拷贝数主要存在于腺癌，EGFR基因突变与EGFR基因拷贝数之间有显著的相关性。结论中国人NSCLC组织具有较高的EGFR基因突变率和FISH阳性率；联合检测EGFR基因拷贝数和基因突变可能更有利于靶向药物的筛选。

Objective To investigate EGFR mutations and gene copy number status in non-small cell lung carcinomas in the Chinese patients. Methods Using formalin fixed and paraffin embedded tissue samples, EGFR mutations were investigated in 290 cases of non-small cell lung carcinomas by micredissection and scorpions amplification refractory mutation system. The status of EGFR gene copy number was investigated by FISH. Furthermore, the relationship between EGFR mutations and gene copy number, and the relationship between EGFR gene status and clinicopathological variables of non-small cell lung carcinoma were analyzed. Results The overall mutation rate of EGFR was 41.7% （121/290）. The mutation rates in adenocarcinoma,large cell carcinoma and squamous carcinoma were 48.4%, 16. 7% and 0,respectively. Ninety-two of 121 cases with mutations had exon 19 deletion and L858R mutation, and 6 tumors contained both types of the mutation. The overall FISH positive rate of EGFR was 51.2% （107/209）. FISH positive rates in adenocarcinoma, large cell carcinoma and squamous carcinoma were 52. 1%, 75.0% and 11.1%, respectively. Therefore, EGFR mutations mainly occurred in the adenocarcinoma, and was significantly correlated with EGFR high copy number. Conclusions There are higher EGFR mutation rate and FISH positive rate in non-small cell lung carcinoma in Chinese patients. Combined analysis of EGFR mutation and gene copy number by FISH may provide a superior approach in selecting patients who may benefit anti-EGFR target therapy.