Prognostic value of MET protein overexpression and gene amplification in locoregionally advanced nasopharyngeal carcinoma

Oncotarget. 2015 May 30;6(15):13309-19. doi: 10.18632/oncotarget.3751.

Abstract

This study assessed the incidence and prognostic value of MET protein overexpression and gene amplification in locoregionally advanced nasopharyngeal carcinoma (NPC). Specimens from 376 consecutive patients with locoregionally advanced NPC were subjected to immunohistochemistry to analyze MET protein expression and fluorescence in situ hybridization to assess MET amplification status. In total, 139/376 (37.0%) patients had MET protein overexpression; of whom, 7/139 (5.0%) had MET amplification. MET overexpression was significantly associated with locoregional failure (P = 0.009), distant metastasis (P = 0.006) and death (P < 0.001); MET amplification was significantly associated with death (P = 0.021). A positive correlation was observed between MET copy number status and MET protein expression (r = 0.629, P < 0.001). Multivariate analysis demonstrated MET overexpression was an independent prognostic factor for overall survival (OS; HR, 1.99; 95% CI, 1.38-2.87; P < 0.001) and disease-free survival (DFS; HR, 1.85; 95% CI, 1.33-2.57; P < 0.001), and MET amplification was independently associated with poorer OS (HR, 4.24; 95% CI, 1.78-10.08; P < 0.001) and DFS (HR, 5.44; 95% CI, 2.44-12.09; P < 0.001). In conclusion, MET protein overexpression and gene amplification are independent prognostic factors for OS and DFS in locoregionally advanced nasopharyngeal carcinoma, and may provide therapeutic biomarkers to identify patients in whom MET inhibitors may be beneficial.

Keywords: MET amplification; MET overexpression; locoregionally advanced nasopharyngeal carcinoma; prognosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biopsy
  • Carcinoma
  • Female
  • Gene Amplification*
  • Gene Expression Regulation, Neoplastic / physiology*
  • Humans
  • In Situ Hybridization, Fluorescence
  • Male
  • Middle Aged
  • Nasopharyngeal Carcinoma
  • Nasopharyngeal Neoplasms / genetics*
  • Nasopharyngeal Neoplasms / mortality
  • Nasopharyngeal Neoplasms / pathology
  • Prognosis
  • Proto-Oncogene Proteins c-met / genetics*

Substances

  • MET protein, human
  • Proto-Oncogene Proteins c-met