title: The Prognostic Significance of c-MET and EGFR Overexpression in Resected Gastric Adenocarcinomas.
abstract: OBJECTIVE
  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).
  
  
  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.
authors.affiliation: Department of Pathology and Laboratory Medicine, Division of Anatomical Pathology, The Ottawa Hospital, University of Ottawa.
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Paliga
authors.affiliation: The Ottawa Hospital Research Institute, Ottawa, ON.
authors.forename: Horia
authors.initials: H
authors.lastname: Marginean
authors.affiliation: Department of Pathology and Laboratory Medicine, The University of British Columbia, Vancouver, BC, Canada.
authors.forename: Basile
authors.initials: B
authors.lastname: Tessier-Cloutier
authors.affiliation: Department of Pathology and Laboratory Medicine, Division of Anatomical Pathology, The Ottawa Hospital, University of Ottawa.
authors.forename: Bibianna
authors.initials: B
authors.lastname: Purgina
authors.affiliation: The Ottawa Hospital Research Institute, Ottawa, ON.
authors.forename: Derek
authors.initials: D
authors.lastname: Jonker
authors.affiliation: Department of Pathology and Laboratory Medicine, Division of Anatomical Pathology, The Ottawa Hospital, University of Ottawa.
authors.forename: Esmeralda C
authors.initials: EC
authors.lastname: Marginean
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002170:Canada; D066246:ErbB Receptors / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009367:Neoplasm Staging; D011379:Prognosis; D016016:Proportional Hazards Models; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism*; D012189:Retrospective Studies; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D015996:Survival Rate; D046888:Tissue Array Analysis
chemical_list: C512478:EGFR protein, human; D066246:ErbB Receptors; C491743:MET protein, human; D019859:Proto-Oncogene Proteins c-met