人表皮生长因子受体2蛋白过表达及基因异常在非小细胞肺癌中的临床意义  

Clinical significance of HER-2 protien overexpression and HER-2 gene dysregulation in non-small cell lung cancer

作　　者：王晓刚[1] 陈振文[1] 郗彦凤[2] 柴菲[1] 徐义荣[1] 李静[2] 孙瑞芳[2] 白玮[2] 

机构地区：[1]山西医科大学汾阳学院病理学教研室,032200 [2]山西省肿瘤医院病理科,太原030013

出　　处：《肿瘤研究与临床》2016年第1期21-27,共7页Cancer Research and Clinic

基　　金：山西省自然科学基金（2011011038-1、2012011038-4）

摘　　要：目的分析非小细胞肺癌（NSCLC）中人表皮生长因子受体2（HER-2）蛋白表达及其基因异常情况与NSCLC临床病理参数和预后的相关性。方法选取山西省肿瘤医院病理科2006年1月至2007年2月手术切除、有详尽病历资料的NSCLC存档石蜡标本140例（鳞状细胞癌89例，腺癌51例），以70例距离肿物5cm正常肺组织作为对照。应用免疫组织化学法检测NSCLC中HER．2蛋白表达，应用荧光原位杂交（FISH）法检测其基因状态。结果在NSCLC组织及正常组织中HER．2蛋白过表达分别有17例（12．14％）及0例，两者差异有统计学意义（P〈0．01）。HER．2蛋白过表达与NSCLC患者的性别、年龄、吸烟史、临床分期、淋巴结转移均无关（均P〉0．05），而与其病理分型有关（Х^2=4．19，P=0．04）。40例（28．57％）HER-2基因拷贝数≥3，包括HER．2基因扩增6例（4．29％），基因多拷贝34例（24．29％）。HER．2基因扩增与病理分型（P=0．024）、吸烟史（P=0．048）及年龄（P=0．015）相关，而与淋巴结转移、性别、临床分期均无关（均P〉0．05）。HER-2基因多拷贝与上述参数均无关（均P〉0．05）。Cox回归分析显示，HER-2蛋白过表达、基因扩增及基因多拷贝与预后均无相关陛（均P〉0．05）。HER．2蛋白过表达与基因扩增相关（P〈0．01），与基因多拷贝不相关（P〉0．05）。结论HER．2蛋白过表达与NSCLC病理分型相关，其在腺癌中表达更强。HER．2基因扩增在腺癌、无吸烟史、低龄患者中发生率更高。HER-2蛋白过表达及基因异常与NSCLC预后无相关性。Objective To investigate the dysregulation of HER-2 protein and gene in non-small cell lung cancer （NSCLC）, and to identify the association between clinicopathological features,prognosis and HER- 2 aberrations amongst protein and gene. Methods 140 NSCLC tissues （89 squamous cell carcinoma, 51 adenocarcinoma） with operative section and detailed case were taken from pathology department of Shanxi Cancer Hospital from Jan 2006 to Feb 2007, while 70 normal tissues were set as control group. Immunohistochemistry was applied to detect the state of HER-2 protein expression,and fluorescence in situ hybridization （FISH） was applied to test the status of gene amplification. Results In normal and NSCLC tissues, over-expression of HER-2 was detected in 0 case and 17 （12.14 %） cases （P 〈 0.05）, respectively. The over-expression of HER-2 was associated with the pathological type of NSCLC, which was detected more frequently in adenocarcinoma （X2 = 4.19, P = 0.04）, rather than the gender, age, smoke history, clinical stages, and lymphatic metastasis of patients. 40 （28.57 %） cases presented HER-2 gene copy number ≥3, including 6 （4.29 %） patients with HER-2 gene amplification, 34 （24.29 %） patients with HER-2 gene multicopy. HER-2 gene amplification was associated with the pathological type （P = 0.024）, smoke history （P = 0.048） and age （P = 0.015）, rather than lymphatic, gender, clinical stages. None clinicopathological features were presented correlation with HER-2 gene multicopy （P 〉 0.05）. There was no significantly difference in survival between patients with and without HER-2 protein over-expression and HER-2 gene dysregulation （P 〈 0.05）. HER-2 protein over-expression was associated with HER-2 gene amplification （P 〉 0.05）, while no relationship between HER-2 protein overexpression and HER-2 gene multicopy （P 〈 0.01）. Conclusions The over-expression of HER-2 is related to pathological type of NSCLC with more frequent expression in adenocarcinoma.

关 键 词：癌 非小细胞肺 受体 表皮生长因子 免疫组织化学 荧光原位杂交 预后 

分 类 号：R734.2[医药卫生—肿瘤]