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

Oncotarget 2018 Februrary 28
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 ( MET amp): MET /CEP7 ≥ 2 or MET -CN ≥ 5; MET -CN-gain ( MET cng): MET -CN ≥ 4 to < 5; and MET -negative ( MET neg): MET -CN < 4. MET amp was associated with high fatality ( P =.036) and stage IV tumors ( P =.038). In patients with stages I-III NSCLC, patients in the MET amp category had the shortest OS ( P =.015) and more often developed distant metastases within 1 year ( P =.004). In patients with stage IV tumors, MET amp did not further impact the OS. Patients in the MET cng category had the longest OS ( P =.053). Multivariate analysis confirmed MET amp 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. MET amp is an independent risk factor predicting early distant metastasis and patients with MET cng could represent a lower-risk group.

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