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The Prognostic Significance of c-MET and EGFR Overexpression in Resected Gastric Adenocarcinomas

Paliga, Aleksandra MD*; Marginean, Horia MD; Tessier-Cloutier, Basile MD; Purgina, Bibianna MD*; Jonker, Derek MD; Marginean, Esmeralda C. MD*

American Journal of Clinical Oncology: December 2017 - Volume 40 - Issue 6 - p 543–551
doi: 10.1097/COC.0000000000000202
Original Articles: Gastrointestinal

Objectives: Epidermal growth factor receptor (EGFR) and c-MET are tyrosine kinase growth factor receptors implicated in gastric cancer (GC), and their pathways appear to be interdependent. The aim of this study was to investigate the prognostic value of EGFR and c-MET protein overexpression by immunohistochemistry in Canadian patients with resected GC and correlate it with clinicopathologic characteristics and overall survival (OS).

Materials and Methods: Tissue microarray blocks were constructed from 120 resected GCs stained with EGFR and c-MET and scored semiquantitatively (0 to 3+). Each receptor’s expression was compared with clinicopathologic characteristics and survival. Descriptive statistics, Kaplan–Meyer, and Cox regression were used for statistical analyses.

Results: Of the 113 interpretable cases, overexpression of EGFR and c-MET was noted in 17 (15%) and 65 (57%), respectively; coexpression of EGFR and c-MET was observed in 12 (10%) of GC. EGFR and c-MET overexpression correlated with poor OS: median 13 versus 30 months in EGFR positive versus negative GC (hazard ratio [HR]=1.67, P=0.11); 27 versus 49 months in c-MET positive versus negative GC (HR=1.17, P=0.49), respectively. GC coexpressing EGFR and c-MET was significantly correlated with poor survival: 12 versus 29 months in double-positive versus rest of tumors both in univariate (HR=2.62, P=0.003) and multivariate analyses (HR=2.58, P=0.01).

Conclusions: This study describes the prevalence and prognostic value of EGFR and c-MET in a Canadian population of patients undergoing curative intent resection for GC. Both c-MET and EGFR overexpression trended toward poor OS, but only the group with EGFR+/c-MET+ GC reached statistical significance on multivariate analysis.

Supplemental Digital Content is available in the text.

*Department of Pathology and Laboratory Medicine, Division of Anatomical Pathology, The Ottawa Hospital, University of Ottawa

The Ottawa Hospital Research Institute, Ottawa, ON

Department of Pathology and Laboratory Medicine, The University of British Columbia, Vancouver, BC, Canada

Supported by the Ottawa Hospital Pathology and Laboratory Medicine (PALM) Academic Enrichment Fund.

The authors declare no conflicts of interest.

Reprints: Esmeralda C. Marginean, MD, Department of Pathology and Laboratory Medicine, Division of Anatomical Pathology, The Ottawa Hospital, University of Ottawa, CCW Rm 4251, 501 Smyth Rd, Ottawa, ON, Canada K1H 8L6. E-mail: cmarginean@toh.on.ca.

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