Research Papers:

MET amplification assessed using optimized FISH reporting criteria predicts early distant metastasis in patients with non-small cell lung cancer

Lianghua Fang, Hui Chen, Zhenya Tang, Neda Kalhor, Ching-Hua Liu, Hui Yao, Shimin Hu, Pei Lin, Jin Zhao, Raja Luthra, Rajesh R. Singh, Mark J. Routbort, David Hong, L. Jeffrey Medeiros, Xinyan Lu _

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Oncotarget. 2018; 9:12959-12970. https://doi.org/10.18632/oncotarget.24430

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Lianghua Fang1,5, Hui Chen2, Zhenya Tang1, Neda Kalhor2, Ching-Hua Liu1,7, Hui Yao3, Shimin Hu1, Pei Lin1, Jin Zhao2,6, Raja Luthra1, Rajesh R. Singh1, Mark J. Routbort1, David Hong4, L. Jeffrey Medeiros1 and Xinyan Lu1,7

1Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

2Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

3Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

4Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

5Department of Oncology, Jiangsu Province Hospital of Traditional Chinese Medicine, Nanjing, Jiangsu, China

6Department of Clinical Laboratory, Hunan Cancer Hospital & The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China

7Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA

Correspondence to:

Xinyan Lu, email: Xinyan.lu@northwestern.edu

Keywords: MET gene amplification; MET FISH reporting criteria; non-small cell lung cancer; distant metastasis

Received: July 02, 2017     Accepted: January 30, 2018     Published: February 07, 2018


To investigate the prognostic impact of MET copy number (MET-CN) in patients with non-small cell lung cancer (NSCLC), we retrospectively reviewed clinical and pathologic data of NSCLC patients whose tumors were assessed for MET-CN using fluorescence in situ hybridization (FISH). We correlated MET-CN status with patient overall survival (OS) and optimized MET-FISH reporting criteria. The study group included 384 patients with NSCLC of which 88% were adenocarcinoma and 55.7% of patients had distant metastases. There were 170 patients with stages I-III and 214 patients with stage IV disease. Based on the MET-CN and MET/CEP7 ratio the patients were classified into 3 categories: MET-amplification (METamp): MET/CEP7 ≥ 2 or MET-CN ≥ 5; MET-CN-gain (METcng): MET-CN ≥ 4 to < 5; and MET-negative (METneg): MET-CN < 4. METamp was associated with high fatality (P=.036) and stage IV tumors (P=.038). In patients with stages I-III NSCLC, patients in the METamp category had the shortest OS (P=.015) and more often developed distant metastases within 1 year (P=.004). In patients with stage IV tumors, METamp did not further impact the OS. Patients in the METcng category had the longest OS (P=.053). Multivariate analysis confirmed METamp to be an independent high-risk factor (HR 3.26; P=.026) and predicted earlier progression to distant metastasis (HR 4.86; P=.001). In conclusion, we suggest that the MET-FISH criteria presented optimizes risk stratification by defining 3 categories of NSCLC patients. METamp is an independent risk factor predicting early distant metastasis and patients with METcng could represent a lower-risk group.

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