Abstract

<div>Abstract<p>MET and its sole ligand, hepatocyte growth factor (HGF), are promising targets in gastric and gastroesophageal junction cancer. We evaluated whether MET protein expression or <i>MET</i> gene amplification is prognostic for overall survival (OS) in Chinese patients with advanced gastric or gastroesophageal junction cancer. Archival formalin-fixed, paraffin-embedded tumor samples from patients with unresectable locally advanced or metastatic gastric or gastroesophageal junction cancer enrolled in clinical trials at Peking University Cancer Hospital from 2008 to 2010 were assessed for MET and phospho-MET (p-MET) expression by immunohistochemistry and <i>MET</i> amplification by FISH. MET-positive expression was defined as membrane protein staining in ≥25% of tumor cells. <i>MET</i> amplification was defined as <i>MET</i>:centromere 7 ratio >2.0. We tested the association of MET status with clinical characteristics and OS, and also evaluated the association between expression and amplification. One hundred sixty-eight patients were eligible. Of the evaluable samples, 53 of 137 (39%) were MET positive, eight of 134 (6%) were p-MET positive, and eight of 113 (7%) were <i>MET</i> amplified. Neither MET expression nor <i>MET</i> amplification were associated with clinical characteristics, except Lauren classification (<i>P</i> = 0.04); <i>MET</i> amplification was associated with diffuse type. No significant OS difference was observed between MET-positive and MET-negative populations, regardless of first-line chemotherapy received. In 95 evaluable patients, MET expression was significantly associated with <i>MET</i> amplification (<i>P</i> < 0.001); all <i>MET</i>-amplified tumor samples showed some MET expression. In 96 evaluable patients, p-MET positivity was significantly associated with <i>MET</i> amplification (<i>P</i> < 0.001). Further evaluation in larger and independent sample sets is warranted to confirm our findings. <i>Mol Cancer Ther; 14(11); 2634–41. ©2015 AACR</i>.</p></div>

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