表皮生长因子受体和肝细胞生长因子受体在非小细胞肺癌中的表达及其与预后的关系

Clinicopathological features and prognostic implications of EGFR/c-Met gene copy number and protein expression in non-small cell lung cancer

目的 探讨非小细胞肺癌（NSCLC）组织中表皮生长因子受体（EGFR）和肝细胞生长因子受体（c-Met）基因和蛋白的表达情况,及其与NSCLC临床病理特征和预后的关系.方法 采用免疫组化法检测61例NSCLC组织中EGFR和c-Met蛋白的表达情况,采用实时荧光定量PCR法检测EGFR和c-Met DNA的相对拷贝数.结果 61例NSCLC组织中,EGFR和c-Met蛋白的阳性表达率分别为77.0%和57.4%.EGFR和c-Met蛋白在高、中分化NSCLC组织中的阳性表达率分别为61.5%和38.5%,均明显低于低分化的肿瘤组织（均P＜0.05）.EGFR和c-Met DNA在吸烟患者中的相对拷贝数分别为0.22±0.22和0.20±0.21,均明显高于不吸烟患者（均P＜0.05）;在腺癌中的相对拷贝数分别为0.24±0.26和0.23±0.25,均明显高于鳞癌患者（均P＜0.05）.EGFR蛋白与c-Met蛋白表达、EGFR DNA相对拷贝数与c-Met DNA相对拷贝数、EGFR蛋白表达与EGFR DNA相对拷贝数之间均具有显著的相关性（均P＜0.05）,但c-Met蛋白表达与c-Met DNA相对拷贝数之间没有相关性（P=0.259）.EGFR DNA低拷贝组和高拷贝组患者的术后中位生存时间分别为48和36个月,差异有统计学意义（P=0.039）;c-Met DNA低拷贝组和高拷贝组患者的术后中位生存时间分别为44和31个月,差异亦有统计学意义（P=0.022）.结论 EGFR和c-Met的蛋白表达与NSCLC的分化程度有关;EGFR和c-Met DNA的相对拷贝数与NSCLC患者的吸烟史以及病理类型有关,有助于预测NSCLC患者的预后.

Objective To investigate the gene copy number and protein expression of EGFR/cMet, so as to explore the relationship between them and the clinicopathological features and prognosis in nonsmall cell lung cancer （NSCLC） patients. Methods The expression of EGFR/c-Met protein was detected by immunohistochemical staining in NSCLC tissues of 61 cases. The level of EGFR/c-Met gene copy number was detected by fluorescent RT-PCR. Results The positive rates of EGFR and c-Met protein expression were 77.5% and 57.4%, respectively. These rates in well/moderately differentiated NSCLC tissues were 61.5% and 38.5%, all significantly lower than the data in poorly differentiated tissues （P 〈0. 05）. The relative EGFR and c-Met gene copy number was 0.22±0.22 and 0.20±0.21 in smokers, respectively, all significantly higher than that in non-smokers （ P 〈 0. 05）. The gene copy number of EGFR and c-Met in adenocarcinoma was 0.24 ± 0.26 and 0.23 ± 0.25, respectively, all higher than the data in squamous cell carcinoma （ P 〈 0. 05 ）. There was a significant correlation in regard to the EGFR and c-Met protein expression, EGFR and c-Met gene copy number, and the protein expression vs. the gene copy number only in EGFR （ P 〈 0. 05 ）. But there was no significant correlation between the c-Met protein expression and gene copy number （ P = 0. 259 ）. There was a statistical significance between the postoperational median survival times （MST） of low EGFR gene copy number （48 months） and the high EGFR gene copy number （36 months） patients （P=0.039）. Similarly, there was also a significant difference between the MST of the low and high c-Met gene copy number patients （44 and 31 months, P=0.022）. Conclusion There is a correlation between the EGFR and c-Met protein expression and the differentiation of NSCLC. The relative gene copy number is correlated with pathologic types and smoking of NSCLC patients, and it can be used in the prediction of prognosis.