非小细胞肺癌EGFR基因突变与扩增及蛋白表达的相关性分析  

Correlation of EGFR gene mutation with its amplification and protein expression in nonsmall cell lung cancer

作　　者：陈顺平[1] 苏海燕[1] 吴文乔[1] 余英豪[2] 刘伟[2] 沈洪武[1] 

机构地区：[1]福建医科大学附属漳州市医院病理科,漳州363000 [2]南京军区福州总医院病理科,福州350025

出　　处：《临床与实验病理学杂志》2015年第6期657-661,665,共6页Chinese Journal of Clinical and Experimental Pathology

基　　金：福建漳州市自然科学基金(ZZ2012J33)

摘　　要：目的 观察非小细胞肺癌（non-small cell lung cancer,NSCLC）发生、发展中表皮生长因子受体（epidermal growth factor receptor,EGFR）基因突变及扩增与蛋白表达的相关性;探讨EGFR基因突变及扩增与NSCLC临床病理特征的关系。方法 应用实时荧光定量PCR（quantitative real-time polymerase chain reaction,qRT-PCR）、荧光原位杂交（fluorescent in situ hybridization,FISH）及免疫组化（immunohistochemistry,IHC）技术同时对NSCLC石蜡包埋组织中EGFR基因（18～21号外显子）突变、扩增及蛋白表达进行检测。结果 qRT-PCR技术检测NSCLC组织中EGFR基因（18～21号外显子）的突变率为58.18%（32/55）,其中19号外显子缺失和21号外显子L858R点突变占87.50%（28/32）;EGFR基因突变与患者性别、吸烟史、组织病理分型有关（P〈0.01）,与患者年龄、淋巴结转移及TNM分期无关（P〉0.05）;EGFR基因扩增率为23.64%（13/55）,EGFR蛋白阳性率为70.91%（39/55）;EGFR基因突变与基因扩增具有一定相关性（P〈0.05）,EGFR这两种基因状态与其蛋白表达无相关性（P〉0.05）。结论 NSCLCEGFR基因突变在女性、无吸烟史及腺癌中表达较高,是酪氨酸激酶抑制剂（tyrosine kinase inhibi-tors,TKI）筛查主要对象;EGFR基因突变与基因扩增具有一定相关性,但基因突变与扩增的先后顺序尚不清楚,需增加病例数进一步探讨;EGFR基因突变和扩增与蛋白表达不一致,原因有待进一步分析。Purpose To investigate the correlation of the epidermal growth factor receptor （EGFR） gene mutation and amplification and protein expression with occurrence and development of non-small cell lung cancer （ NSCLC）, and to explore the relationship be- tween the mutation and amplification of EGFR gene and other clinical pathological parameters. Methods qRT-PCR, FISH and immu- nohistochemistry were used to detect EGFR gene （exons 18, 19, 20 and 21 ） mutation, amplification and protein expression in paraf- fin-embedded tissues of NSCLC. Results EGFR gene （exons 18, 19, 20 and 21 ） mutation rate was 58.18% （32/55） in NSCLC with qRT-PCR technology, in which the occurrence rate of exon 19 deletions and exon 21 mutation of IB58R was 87. 50% （28/32）. EGFR gene mutation rate was significantly different in gender, smoking history and pathological type （P 〈 0.01 ）, but no statistical sig- nificance in age, lymph node metastasis and TNM staging （P 〉 0. 05）. EGFR gene amplification rate was 23.64% （13/55） and its protein expression rate was 70. 91% （39/55）. Both EGFR gene mutation and amplification was closely correlated （P 〈0. 05）, but the two states of EGFR gene and its protein expression had no correlation （P 〉 0. 05）. Conclusion EGFR gene mutation with high pro- tein expression of NSCLC is commonly found in female, no-smoking and adenocarinoma patients, who are main candidates of a tyrosine kinase inhibitor （TKI） screening. EGFR gene mutation and amplification is typically correlated, but their consequence is unknown, which needs to be further investigated. EGFR gene mutation and amplification is not consistent with protein expression, its underlying machanism is to be determined.

关 键 词：肺肿瘤 非小细胞肺癌 表皮生长因子受体 PCR FISH 免疫组织化学 

分 类 号：R734.2[医药卫生—肿瘤]