title: EGFR family and cMet expression profiles and prognostic significance in esophagogastric adenocarcinoma.
abstract: BACKGROUND
  Targeted therapy with anti-human epidermal growth factor receptor-2 (HER2) monoclonal antibody in patients with HER2 overexpressed esophagogastric adenocarcinoma (EGA) improves survival; however, the effect is transient due to the development of resistance. Some studies suggest that cMet overexpression provides cross talk for epidermal growth factor receptor (EGFR) and HER2 inhibition. We sought to characterize the expression profile of the EGFR family and cMet receptors in untreated, resected EGA.
  
  
  METHODS
  This retrospective analysis included all sequential patients with esophageal or gastroesophageal junction (GEJ) adenocarcinoma who underwent primary resection, without neoadjuvant therapy or HER2 inhibition, with adequate tissue, at the University of Florida from 2001 to 2011. Central blinded immunohistochemistry (IHC) was performed on tumor specimens with EGFR, HER2, HER3, HER4 and cMet expression scored as low (0, 1+) or high (2+, 3+). Demographic and tumor characteristics were compared using Fisher exact test. Kaplan-Meier curves and univariate analysis compared survival among different receptors.
  
  
  RESULTS
  Total 52 patients were included in the study with median age 66 years. High expression of EGFR (73%), HER2 (40%), HER3 (75%), HER4 (35%) and cMet (69%) was detected among the study group. HER3 and HER4 co-expression was found in 18 (35%) cases. Pan expression of all four EGFR family members with cMet was noted in only 17% of cases. On univariate analysis, tumor stage and depth correlated with survival, while cMet + HER3 +/- EGFR receptor co-expression trended towards a worse survival.
  
  
  CONCLUSIONS
  EGFR family and cMet are frequently co-expressed in treatment naïve resected EGA or GEJ tumors. Although our data do not significantly show receptor status as a prognostic factor, the co-expression profiles support for further investigation to improve targeting of this signal transduction axis.
authors.affiliation: Division of Hematology & Oncology, Department of Medicine, College of Medicine, Gainesville, FL, USA.
authors.forename: Ellie
authors.initials: E
authors.lastname: Chan
authors.affiliation: Department of Pathology, Immunology and Laboratory Medicine, College of Medicine, Gainesville, FL, USA.
authors.forename: Ahmad
authors.initials: A
authors.lastname: Alkhasawneh
authors.affiliation: Department of Pathology, Immunology and Laboratory Medicine, College of Medicine, Gainesville, FL, USA.
authors.forename: Lizette Vila
authors.initials: LV
authors.lastname: Duckworth
authors.affiliation: Division of Hematology & Oncology, Department of Medicine, College of Medicine, Gainesville, FL, USA.
authors.forename: Tabish
authors.initials: T
authors.lastname: Aijaz
authors.affiliation: Department of Pathology, Immunology and Laboratory Medicine, College of Medicine, Gainesville, FL, USA.
authors.forename: Tania Zuluaga
authors.initials: TZ
authors.lastname: Toro
authors.affiliation: Department of Biostatistics, College of Medicine, Gainesville, FL, USA.
authors.forename: Xiaomin
authors.initials: X
authors.lastname: Lu
authors.affiliation: Department of Surgery University of Florida, College of Medicine, Gainesville, FL, USA.
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Hughes
authors.affiliation: Department of Pathology, Immunology and Laboratory Medicine, College of Medicine, Gainesville, FL, USA.
authors.forename: Amy
authors.initials: A
authors.lastname: Collinsworth
authors.affiliation: Division of Hematology & Oncology, Department of Medicine, College of Medicine, Gainesville, FL, USA.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: George
keywords: Esophageal cancer; HER3; HER4; epidermal growth factor receptor (EGFR); esophagogastric adenocarcinoma (EGA); gastric cancer; hepatocyte growth factor receptor (cMet); human epidermal growth factor receptor-2 (HER2)