Correlation among genetic variations of c-MET in Chinese patients with non-small cell lung cancer
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Jianchun Duan1,*, Xiaodan Yang2,*, Jun Zhao2, Minglei Zhuo2, Zhijie Wang1, Tongtong An2, Hua Bai1 and Jie Wang1
1Department of Medical Oncology, Cancer Hospital Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
2Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Department of Thoracic Medical Oncology, Beijing Cancer Hospital and Institute, Beijing, China
*These authors contributed equally to this work
Jie Wang, email: [email protected]
Hua Bai, email: [email protected]
Keywords: non-small-cell lung cancer; c-MET; protein expression; copy number; mutation
Abbreviations: NSCLC: Non-Small-Cell Lung Cancer; GCN: gene copy number; IHC: Immunohistochemistry; FISH: fluorescent In Situ Hybridization; DHPLC: Denaturing High Performance Liquid Chromatography
Received: September 07, 2017 Accepted: December 15, 2017 Published: December 20, 2017
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 IHC2+ staining, 35.5% was FISH positive, while cases with IHC3+ 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- In-Situ-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.
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