MET Expression Plays Differing Roles in Non-Small-Cell Lung Cancer Patients with or without EGFR Mutation

Introduction: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors and Met inhibitors have enabled progress in the management of advanced non-small-cell lung cancer (NSCLC). However, the clinical benefits of these agents are not uniform across the NSCLC spectrum. Thus, we evaluated the prognostic effect of mesenchymal-epithelial transition (MET) expression in Asian NSCLC patients with or without EGFR mutation. Methods: Frozen tumor tissues were collected from 92 patients with surgical resection and 10 with lymph node biopsy. Mutations in exons 18-21 in the EGFR-tyrosine kinase domain and MET expression were analyzed by using sequencing and immunohistochemistry, respectively. Results: The MET overexpression rate was 51% in NSCLC patients. MET-positive patients had poorer overall survival than MET-negative patients (29.8 versus 69.1 months, chi(2) = 7.420, p = 0.006) in patients with wild-type EGFR. However, no statistically significant difference was found in EGFR mutant patients (35.0 versus 35.9 months, chi(2) = 0.114, p = 0.735). Multivariate analysis showed that stage, MET expression, and sex were independent prognostic factors in patients with wild-type EGFR (chi(2) = 32.896, p < 0.001). Conclusions: These results suggest that MET expression has different prognostic significance in patients with differing EGFR mutation status. Whether MET inhibitors should be given early to NSCLC patients with EGFR wild-type needs further investigation.