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.
Highlights
Chromosomal aneuploidy or somatic copy number alterations (SCNAs) are frequently observed in malignant neoplasms including lung cancers and have been proposed to drive tumorigenesis or treatment resistance [1, 2]
We evaluated data on mesenchymal-epithelial transition factor gene (MET)-CN status in 384 non-small cell lung cancer (NSCLC) patients with various disease stages and identified associations between MET copy number (MET-CN) and clinical outcome
To resolve the conflicting MET-fluorescence in situ hybridization (FISH) reporting criteria in the literature, we stratified our patient cohort into 5 groups based on MET-CN and MET/CEP7 ratio and identified associations between these groups and outcomes
Summary
Chromosomal aneuploidy or somatic copy number alterations (SCNAs) are frequently observed in malignant neoplasms including lung cancers and have been proposed to drive tumorigenesis or treatment resistance [1, 2]. MET amplification (METamp) has been associated with shorter overall survival (OS) in patients with non-small cell lung cancer (NSCLC) [3,4,5,6]. Under the optimized MET-FISH reporting criteria, the median OS durations of early-stage patients with METamp, METcng, and METneg were 28.1, 134.4, and 51.6 months, respectively.
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