非小细胞肺癌免疫组化指标的表达与EGFR基因突变的相关性  

Correlation of TS,ERCC1,β-tubulin-Ⅲ and RRM1 expressions with EGFR mutations in non-small cell lung cancer

作　　者：邢舴[1] 呼群[1] 苏乌云[1] 赵海燕[1] 王华[2] 张称心[3] 

机构地区：[1]内蒙古医科大学附属医院肿瘤内科,呼和浩特医学博士研究生010000 [2]内蒙古呼和浩特市第一医院肿瘤内科,呼和浩特010050 [3]内蒙古医科大学附属医院儿科,呼和浩特010000

出　　处：《医学研究生学报》2017年第3期275-278,共4页Journal of Medical Postgraduates

基　　金：国家自然科学基金(81160253)

摘　　要：目的目前靶向治疗已经是晚期非小细胞肺癌(NSCLC)表皮生长因子(EGFR)突变者的首选治疗方案,但关于免疫组化相关指标与EGFR基因突变之间的关系研究较少。文中旨在分析NSCLC组织中人类胸苷酸合成酶(TS)、切除修复互补交叉基因1(ERCC1)、β-微管蛋白Ⅲ(β-tubulin-Ⅲ)和核糖核苷酸还原酶亚单位1(RRM1)的表达与EGFR基因突变的关系。方法选取2014年6月至2015年12月初诊于内蒙古医科大学附属医院肿瘤内科并行EGFR突变检测的336例肺癌患者,进行EGFR 29种基因突变检测,EGFR基因存在突变的患者则为突变组,而无基因突变的患者则为无突变组。采用免疫组化的方法进行TS、ERCC1、β-tubulin-Ⅲ和RRM1蛋白的染色,比较2组肺癌组织中上述4种蛋白的表达差异。结果突变组患者138例(41.07%),无突变组患者198例(58.93%)。突变组、无突变组患者TS和β-tubulin-Ⅲ的表达差异有统计学意义(9.42%vs 39.39%、44.2%vs 60.1%,P<0.05)。EGFR突变与TS低表达、β-tubulin-Ⅲ低表达相关(r=-0.332、-0.157,P<0.05)。多因素回归分析结果显示,女性患者EGFR突变的风险是男性患者2.109倍[OR=2.109、95%CI:1.268~3.509],腺癌患者EGFR突变的风险是腺鳞癌的24.265倍[OR=24.265,95%CI:3.508~167.845],鳞癌患者EGFR突变的风险是腺癌的15.2倍[OR=15.200,95%CI:4.480~51.569],肺穿刺患者EGFR突变发生是手术患者的2.364倍[OR=2.364,95%CI:1.266~4.413],TS低表达的患者EGFR突变的风险是高表达患者的6.171倍[OR=6.171,95%CI:3.145~12.109]。结论 NSCLC组织中TS和β-tubulin-Ⅲ的低表达可以提示EGFR基因的突变。Objective Currently, the targeted therapy is the first-choice treatment of advanced non-small cell lung cancer （NSCLC） in with epidermal growth factor receptor （ EGFR ） mutations, but few studies have been reported on the relationship between immunohistochemical markers and the EGFR mutation. The aim of thisstudy is to analyze the relationship of the EGFR mutation with the expressions of thymidylate synthetase （TS） , excision repair cross- com-reductase large subunit-1 （RRM1） in NSCLC. Methods We retro-Medical Oncology, the Affiliated Hospital of Inner Mongolia Medicalplementation group 1 （ ERCC1 ）,β- tubulin- Ⅲ, and ribonucleofidespectively analyzed 336 cases of NSCLC treated in the Department ofUniversity, from June 2014 to December 2015 and examined 29 EGFR mutations. We divided the patients into a mutation and a non-mutation group, performed immunohistochemical staining of the TS, ERCC1, β- tubulin- Ⅲ and RRM1 proteins and compared their expressions in the NSCLC tissue between the two groups. Results EGFR mutations were found in 138 （41.07%） of the 336 NSCLC patients but not in the other 198 （58.93%）. The expression of TS was significantly lower in the mutation than in the non-mutation group （9.42% 仍 39.39%,P〈0 .0 5 ） , and so was that of β- tubulin- Ⅲ （44.2% vs 60.1%, P〈0.05）. EGFR mutations were correlated with decreased expressions of TS （ r = -0 .3 3 2 , P〈0.05） and β- tubulin- Ⅲ （r =-0.157, P〈0.05）. Multivariate regression analysis showed that the risk of EGFR mutations was 2.109 times higher in the female patients than in the males （ OR = 2.109, 95% CI： 1.268-3.509） , 24.265 times higher in the adenocarcinoma than in the adeno-squamous carcinoma patients （OR = 24.265, 95% CI： 3.508-167.845） , 15.2 times higher in the squamous carcinoma than in the adenocarcinoma patients （OR=15.200, 95% CI： 4 .4 8 0 -5 1 .5 6 9 ） ,

关 键 词：非小细胞肺癌 人类胸苷酸合成酶 切除修复互补交叉基因1 β-微管蛋白Ⅲ 核糖核苷酸还原酶亚单位1 表皮生长因子 

分 类 号：R734.2[医药卫生—肿瘤]