MET amplification assessed using optimized FISH reporting criteria predicts early distant metastasis in patients with nonsmall 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*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)12959-12970
Number of pages12
JournalOncotarget
Volume9
Issue number16
DOIs
StatePublished - 2018

Keywords

  • Distant metastasis
  • MET FISH reporting criteria
  • MET gene amplification
  • Non-small cell lung cancer

ASJC Scopus subject areas

  • Oncology

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