中文摘要：

背景与目的现有的研究表明表皮生长因子受体（EGFR）相关信号通路在肺癌的发生和发展中起重要作用。EGFR酪氨酸激酶抑制剂（EGFR-TKIs）是目前针对EGFR治疗非小细胞肺癌（NSCLC）的重要分子靶向药物。EGFR的不同存在状态（基因突变和基因扩增）与TKIs的疗效相关。本研究旨在探讨非小细胞肺癌患者中EGFR的存在状态及其临床意义,从而为肺癌病人＂个体化分子治疗＂提供依据。方法研究对象为187例NSCLC病例。用Real-timePCR技术检测EGFR基因19、21外显子的突变状态;用荧光原位杂交（FISH）技术检测EGFR基因的扩增情况,并进一步分析EGFR基因的突变和扩增与患者临床病理生理特征的关系。结果FISH结果显示,47.6%（98/187）的肺癌患者存在EGFR基因的扩增,而EGFR基因的扩增与患者的年龄、性别、组织学类型、吸烟状态及是否存在转移无关（P〉0.05）;Real-timePCR结果显示：20.3%（38/187）的肺癌患者存在EGFR外显子19、21的突变。EGFR基因突变率在女性（32.3%vs14.4%男性）、腺癌（35.5%vs9.9%非腺癌）、不吸烟（38.2%vs10.1%吸烟）患者中明显高（P〈0.05）。EGFR基因扩增与基因突变之间具有一定的相关性,在早期肺癌、腺癌及非吸烟的女性患者中,EGFR基因外显子突变常同时伴有EGFR基因的扩增。有EGFR基因突变或/和基因扩增的患者生存期均高于无EGFR基因异常者,但是没有统计学差异（P〉0.05）。有EGFR基因突变的患者易对TKIs治疗有效。结论EGFR基因突变率在不同的NSCLC患者中不同,其中,在女性、腺癌和不吸烟患者中突变率高;EGFR基因扩增与患者的性别、组织类型、吸烟状态等临床特征无明显关系,与患者预后的相关性有待进一步研究。

英文摘要：

Background and objective It has been demonstrated that epidermal growth factor receptor （EGFR） signal pathway had an important role in the oncogenesis and development of non-small cell lung cancer （NSCLC）. Small-molecule tyrosine kinase inhibitors （TKIs） that target at the kinase domain of EGFR are recently developed target therapy reagents for treatment of NSCLC patients. Previous studies revealed that different patient groups response differently to EGFR-TKI, which is based on the EGFR gene status. The aim of this research was to define the clinicopathologic features associated with the gene amplification and mutation status of the EGFR gene in NSCLC patients and determine the most likely population to benefit from TKI treatment. Methods 187 of NSCLC cases were collected. The mutation status of EGFR exon 19 and 21 were determined by Real-time PCR, as well as the gene amplification status of EGFR gene by FISH. The relationship between EGFR mutation and gene amplification and the clinical pathologic features were analyzed with χ2 test. Results EGFR gene amplifications were identified in 89 of 187 samples （47.6%）. EGFR gene amplification was not associated with age, gender, pathological type, smoking status and metestasis status （P〉0.05）. 20.3% （38/187） of NSCLC patients had EGFR gene mutation. EGFR gene mutation rates were significantly higher in the female （32.3% vs 14.4% male）, non-smoker （38.2% vs 10.1% smoker） and patients with adenocarinoma （35.5% vs 9.9% non-adenocarcinoma） （P〈0.05）. There was a correlation between EGFR gene mutation and gene amplification （P=0.012）, especially in the early stage, adenocarcinoma and never smoking female patients. The patients with EGFR gene mutation and/or gene amplification had longer overall survival than those without, but had no significant difference （P〉0.05）. The patients with EGFR gene mutation had a better response to TKIs therapy than those without. Conclusion The EGFR gene mutation rate is different in the pat