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

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

Yingqin Li  1 , Wenfei Li  1 , Qingmei He  1 , Yafei Xu  1 , Xianyue Ren  1 , Xinran Tang  1 , Xin Wen  1 , Xiaojing Yang  1 , Ying Sun  1 , Jing Zeng  2 , Jingping Yun  2 , Na Liu  1 , Jun Ma  1
Affiliations

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

Yingqin Li et al. Oncotarget. .

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.

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Conflict of interest statement

CONFLICTS OF INTEREST

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1. Representative images of immunohistochemical (IHC) staining for MET in locoregionally advanced nasopharyngeal carcinoma
A. MET IHC score of 0. B. MET IHC score of 1+. B. MET IHC score of 2+. C. MET IHC score of 3+.
Figure 2
Figure 2. Evaluation of MET gene copy number status in patients with high MET expression in locoregionally advanced nasopharyngeal carcinoma using FISH
A–F. Representative images of tumors with MET disomy A. low trisomy B. high trisomy C. low polysomy D. high polysomy E. and MET amplification F.
Figure 3
Figure 3. Kaplan-Meier overall survival and disease-free survival curves for patients with nasopharyngeal carcinoma stratified by MET protein expression and MET amplification status
A–B. Overall survival and disease-free survival curves for patients stratified by MET protein expression. C–D. Overall survival and disease-free survival curves for patients with high MET expression stratified by MET amplification status. Hazard ratios (HRs) were calculated using the unadjusted Cox proportional hazards model; P-values were calculated using the unadjusted log-rank test. CI, confidence interval.
See this image and copyright information in PMC

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