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中国非小细胞肺癌患者中c-MET基因变异的相关性

Correlation among genetic variations of c-MET in Chinese patients with non-small cell lung cancer.

作者信息

Duan Jianchun, Yang Xiaodan, Zhao Jun, Zhuo Minglei, Wang Zhijie, An Tongtong, Bai Hua, Wang Jie

机构信息

Department of Medical Oncology, Cancer Hospital Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Department of Thoracic Medical Oncology, Beijing Cancer Hospital and Institute, Beijing, China.

出版信息

Oncotarget. 2017 Dec 20;9(2):2660-2667. doi: 10.18632/oncotarget.23474. eCollection 2018 Jan 5.

Abstract

BACKGROUND

The purpose of our research was to determine the correlation of amplification, protein expression and somatic mutation of c-MET in IIIb-IV stage NSCLC (Non-small cell lung cancer). We also explored correlation of c-MET variation with clinical outcome.

RESULTS

c-MET expression was observed in 28.6% (56/196) cases, and among those 13.8% (27/196) were shown to be FISH positive. Only 2.67% patients in this study carried the c-MET mutation. Cases with c-MET FISH positive were all IHC positive ,but in IHC positive cases, only half were FISH positive. Among patients with IHC staining, 35.5% was FISH positive, while cases with IHC staining,64% was FISH positive. Both protein expression and copy number of c-MET did not significantly correlate with clinical prognosis in these patients treated with EGFR-TKIs.

CONCLUSIONS

IHC could be used as a preliminary screening method for c-MET copy number amplification and should be confirmed by FISH only in IHC positive case which facilitate selection of ALK or MET inhibitor therapy.

METHODS

c-MET gene copy number, protein expression and somatic mutation for exon 14 were detected by fluorescent- -Hybridization (FISH), Immunohistochemistry (IHC), and Denaturing-High-Performance-Liquid-Chromatography (DHPLC), respectively, in 196 NSCLC patients. The relationship between c-MET abnormalities and clinical outcome of targeted therapy was analyzed by McNemar's test.

摘要

背景

我们研究的目的是确定Ⅲb-Ⅳ期非小细胞肺癌(NSCLC)中c-MET的扩增、蛋白表达和体细胞突变之间的相关性。我们还探讨了c-MET变异与临床结局的相关性。

结果

在196例病例中,28.6%(56/196)观察到c-MET表达,其中13.8%(27/196)为FISH阳性。本研究中只有2.67%的患者携带c-MET突变。c-MET FISH阳性的病例均为免疫组化(IHC)阳性,但在IHC阳性病例中,只有一半为FISH阳性。在IHC染色的患者中,35.5%为FISH阳性,而在IHC未染色的病例中,64%为FISH阳性。在接受表皮生长因子受体酪氨酸激酶抑制剂(EGFR-TKIs)治疗的这些患者中,c-MET的蛋白表达和拷贝数均与临床预后无显著相关性。

结论

免疫组化可作为c-MET拷贝数扩增的初步筛查方法,仅在IHC阳性病例中需通过FISH进行确认,这有助于选择ALK或MET抑制剂治疗。

方法

分别采用荧光原位杂交(FISH)、免疫组化(IHC)和变性高效液相色谱(DHPLC)检测196例NSCLC患者的c-MET基因拷贝数、蛋白表达和第14外显子的体细胞突变。采用McNemar检验分析c-MET异常与靶向治疗临床结局之间的关系。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c91a/5788667/91e917014d6e/oncotarget-09-2660-g001.jpg

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