非小细胞肺癌EGFR突变与磷酸化信号传导蛋白表达的关系

The Relationship between EGFR Gene Mutation and Expression of Downstream Phosphorylated Signal Transduction Proteins in Non-Small Cell Lung Carcinoma

目的:探讨非小细胞肺癌(NSCLC)患者表皮生长因子受体(EGFR)基因突变与其下游磷酸化信号通路蛋白表达的关系。方法:利用PCR和基因测序检测NSCLC患者EGFR第19和21外显子突变,辅以免疫组化染色检测下游信号传导蛋白p-Akt、p-ERK1/2和p-STAT3的表达。结果:66例NSCLC中有11例发生EGFR突变,女性和伴细支气管肺泡特征的腺癌突变率较高。p-Akt、p-ERK1/2和p-STAT3的表达阳性率分别为54.5%、25.8%和33.3%,EGFR突变患者p-Akt阳性率(81.8%)显著高于无突变者(49.1%,P<0.05),且在伴细支气管肺泡特征的腺癌中呈高表达,两者之间p-ERK1/2和p-STAT3表达差异无统计学意义;p-ERK1/2表达与患者年龄相关,p-STAT3在腺癌、小肿瘤(≤3cm)和I期NSCLC中的表达均显著上调(P<0.05)。结论:EGFR突变后的下游信号传导主要以激活Akt途径为主,检测下游信号传导蛋白表达是EGFR基因检测的重要补充,对NSCLC基因分型、疗效监测及预后评估具有重要意义。

Objective： To investigate the relationship between the gene mutation of epithelial growth factor receptor （EGFR） and the expression of its downstream phosphorylated signal transduction proteins in non-small cell lung carcinoma （NSCLC）. Methods：Sixty-six NSCLC patients were performed with the PCR-based sequence analysis on the exon 19 and 21 of EGFR and immunohistochemistry staining to evaluate the expression of phosphorylated Akt, ERK1/2 and STAT3. Results： The EGFR mutation was found in 11 patients （16.7%）. And more women patients with adenocareinomas with bronchiolo- alveolar features （ABAF） and the patients with higher active Akt staining were found the mutation. The positive expressions of phosphorylated Akt, ERK1/2 and STAT3 were detected in 54.5%, 25.8% and 33.3% of tumors, respectively. The higher expression of phosphorylated-Akt was observed in ABAFs, as well as higher expression of phosphorylated-ERK1/2 in elders, and phosphorylated-STAT3 in adenocarcinomas, smaller tumors and lower TNM stages. Conclusion： The results suggested that cells with mutant EGFR survived mainly through the activation of the Akt pathway rather than the ERK and/or STAT3 pathways. This specific property could be an important＇step in multistage cancer progression. The activation of the downstream transduction proteins had important correlation with tumor phenotype and the clinical features in NSCLC patients.