Ⅰ～Ⅲ期肺腺癌组织中EGFR基因突变与ERCC1和RRM1蛋白表达的关系

The relationship between EGFR gene mutation and the expressions of ERCC1 and RRM1 proteins in stagesⅠ-Ⅲ lung adenocarcinoma tissues

目的:探讨Ⅰ～Ⅲ期肺腺癌组织中表皮生长因子受体(epidermal growth factor receptor,EGFR)基因突变与切除修复交叉互补蛋白1(excision repair cross-complementation group1,ERCC1)和核苷酸还原酶亚单位M1(ribonucleotide reductase subunit M1,RRM1)蛋白表达的关系。方法:应用扩增阻滞突变系统在荧光定量PCR仪上检测99例Ⅰ～Ⅲ期肺腺癌组织中EGFR基因19和21外显子的突变情况,应用免疫组织化学法检测其ERCC1和RRM1蛋白的表达。结果:肺腺癌患者中EGFR基因突变率为46.5%,在女性和不吸烟患者中较高(P<0.05);ERCC1蛋白高表达患者50例(50.5%),RRM1蛋白高表达患者52例(52.5%)。与未检测到EGFR基因突变的肺腺癌患者比较,EGFR基因突变患者ERCC1蛋白低表达者多见(P=0.035);肺腺癌组织中,EGFR基因突变与RRM1蛋白表达水平无关(P>0.05);ERCC1蛋白表达水平与RRM1蛋白表达水平无关(P>0.05)。结论:肺腺癌组织中EGFR突变者ERCC1蛋白倾向低表达,这类患者可能更能从以铂类为基础的化疗中受益。

Objective： To investigate the relationship between the mutation of EGFR （epidermal growth factor receptor） gene and the expressions of ERCC1 （excision repair cross-complementation group 1） and RRM1 （ribonucleotide reductase M1） proteins in adenocarcinomatissues from patients with stages Ⅰ-Ⅲ lung adenocarcinoma. Methods： The status ofEGFR gene mutation in exons 19 and 21 in adenocarcinoma tissues from 99 patients with stages Ⅰ-Ⅲ lung adenocarcinomawas detected by amplification refractory mutation system using fluorescence-based quantitative-PCR instrument. The expressions of ERCC1 and RRM1 proteins were detected by immunohistochemistry. Results： The mutation rate ofEGFR gene in all patients was 46.5%. The females or the non-smokers had a higher mutation rate of EGFR gene （P 〈 0.05）. A high expression level of ERCC1 protein was found in 50.5% of patients （50/99）, and a high expression level of RRM1 protein was also found in 52.5% of patients （52/99）. A low expression level of ERCC1 protein was more likely to be seen in patients with EGFR mutation as compared with the patients without EGFR mutation （P = 0.035）, but there was no significant relationship between EGFR mutation and the expression level of RRM1 protein （P 〉 0.05）. There was also no relationship between the expressions of ERCC1 and RRM1 proteins （P 〉 0.05）. Conclusion： A low level of ERCC1 protein is more likely to be expressed in lung adenocarcinoma patients with EGFR mutation, who may benefit from the platinumbased chemotherapy.