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中国非小细胞肺癌患者中MET基因扩增及过表达与表皮生长因子受体(EGFR)无突变的关系

MET Gene Amplification and Overexpression in Chinese Non-Small-Cell Lung Cancer Patients Without EGFR Mutations.

作者信息

Song Zhengbo, Wang Xuzhou, Zheng Yuhui, Su Haiyan, Zhang Yiping

机构信息

Department of Medical Oncology, Zhejiang Cancer Hospital, Hangzhou, China; Key Laboratory Diagnosis and Treatment Technology on Thoracic Oncology, Hangzhou, China.

Department of Pathology, Fuzhou General Hospital of Nanjing Military Command, Fuzhou, China.

出版信息

Clin Lung Cancer. 2017 Mar;18(2):213-219.e2. doi: 10.1016/j.cllc.2016.09.011. Epub 2016 Oct 5.

Abstract

BACKGROUND

The prevalence and clinical pathologic characteristics of MET amplification and overexpression in Chinese patients with non-small-cell lung cancer (NSCLC) remain unknown. In this multicenter study, we sought to reveal the frequency and clinical pathologic characteristics of MET amplification and to explore the predictive value of MET amplification and overexpression status in relation to survival in Chinese NSCLC patients.

PATIENTS AND METHODS

MET amplification was detected by fluorescence in-situ hybridization in 791 patients with EGFR wild-type samples. MET protein expression was detected by immunohistochemistry.

RESULTS

In total, 8 of 791 NSCLC patients with EGFR wild type patients were identified as harboring MET amplification. Among these 8 patients, 1 had adenosquamous carcinoma histology and 7 adenocarcinoma. There was no statistically significant difference among age, sex, smoking status, and histologic type between patients with and without MET amplification. MET amplification was more frequent in advanced-stage disease and in the solid predominant subtype of adenocarcinoma. MET protein expression was performed in 395 patients, and 138 were positive. Patients positive for MET protein expression had worse overall survival (OS) compared to those without MET protein expression (45.0 vs. 65.8 months; P = .001). Multivariate analysis revealed that MET expression was an independent prognostic factor for poor OS (R = 1.497, P = .017), while MET amplification had weak relevance for OS (hazard ratio = 1.974, P = .251).

CONCLUSION

MET amplification was rare in Chinese NSCLC patients without EGFR mutation, with a prevalence of about 1%. MET expression but not amplification could be an independent prognostic factor for shorter OS among these EGFR wild-type NSCLC patients.

摘要

背景

在中国非小细胞肺癌(NSCLC)患者中,MET扩增和过表达的发生率及临床病理特征尚不清楚。在这项多中心研究中,我们试图揭示MET扩增的频率和临床病理特征,并探讨MET扩增和过表达状态对中国NSCLC患者生存的预测价值。

患者与方法

采用荧光原位杂交技术检测791例表皮生长因子受体(EGFR)野生型样本患者的MET扩增情况。采用免疫组织化学法检测MET蛋白表达。

结果

在791例EGFR野生型NSCLC患者中,共8例被鉴定为存在MET扩增。在这8例患者中,1例为腺鳞癌组织学类型,7例为腺癌。MET扩增患者与未扩增患者在年龄、性别、吸烟状态和组织学类型方面无统计学显著差异。MET扩增在晚期疾病和腺癌实性为主亚型中更为常见。对395例患者进行了MET蛋白表达检测,其中138例为阳性。与无MET蛋白表达的患者相比,MET蛋白表达阳性的患者总生存期(OS)更差(45.0个月对65.8个月;P = 0.001)。多因素分析显示,MET表达是OS不良的独立预后因素(R = 1.497,P = 0.017),而MET扩增与OS的相关性较弱(风险比 = 1.974,P = 0.251)。

结论

在中国无EGFR突变的NSCLC患者中,MET扩增罕见,发生率约为1%。在这些EGFR野生型NSCLC患者中,MET表达而非扩增可能是OS缩短的独立预后因素。

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