表皮生长因子受体基因在非小细胞肺癌中的突变情况及蛋白表达情况

Study of EGFR gene mutations and its protein expression in non-small cell lung cancer

目的本研究旨在探讨非小细胞肺癌（NSCLC）患者中表皮生长因子受体（EGFR）基因突变的情况,分析EGFR蛋白表达情况对吉非替尼治疗的指导意义。方法收集140例非小细胞肺癌患者新鲜组织,采用荧光定量PCR法检测EGFR基因突变的状态;同时采用免疫组化SP法检测EGFR蛋白的表达。结果 140例患者中,46例患者发生了EGFR基因突变,其基因突变率为33%,主要发生在19号外显子（20例,43.5%）和21号外显子（23例,50.0%）。腺癌突变发生率为50.6%,腺鳞癌突变发生率为87.5%,鳞癌突变发生率为2.5%,大细胞癌突变发生率为5.3%（P=0.000）,无吸烟史患者突变率为50%,有吸烟史患者的突变率为20.0%（P=0.005）,女性患者突变率为50.0%,男性患者突变率为23.3%（P=0.001）。EGFR蛋白表达阳性组患者的中位无疾病进展生存时间为9个月（95%CI：7.3~10.6个月）,EGFR蛋白表达阴性组患者的中位无疾病进展生存时间为5个月（95%CI：3.5~6.4个月）。结论 EGFR基因突变和EGFR蛋白表达情况联合检测对于筛选EGFR酪氨酸激酶抑制剂（TKI）治疗敏感人群有帮助,并且也能够帮助预测吉非替尼对于晚期NSCLC的疗效及预后。

Objective This study investigated gene mutations of EGFR in Chinese patients with NSCLC,analyzed the protein expression of EGFR and its clinical signify cancer after the treatment of gefitinib. Methods Fluorescent quantitative PCR was used to detect the EGFR gene mutations status, immunohistochemistry was used to detect EGFR protein expression. Results The frequency of EGFR mutations, which were mainly located in exon 19（20 cases,43.5%） and exon 21（23 cases, 50.0%）, was 33%.The mutation frequency of adenocarcinoma, adenosquamous carcinoma, squamous carcinoma and large cell carcinoma was 50.6%, 87.5%, 2.5% and 5.3%（P=0.000）. The mutation frequency of the patients with no smoking history was 50.0%,by contrast, the mutation frequency of the patients who have a history of smoking was 20.0%（P=0.005）. The mutation frequency of the female patients was 50.0%, and the male patients was 23.3%（P=0.001）. The median PFS（Progression Free Survival） of patients whose EGFR protein expression was positive was nine months（95% CI： 7.3-10.6 months）, and the median PFS of the patiens whose EGFR protein expression was negative was five months（95% CI： 3.5-6.4 months）. Conclusion Combined detection of EGFR and protein expression of EGFR can help determined whether the patients may benefit more from EGFR tyrosine kinase inhibitor（EGFR-TKD and also help predict the response and prognosis of gefitinib.