EGFR family and c-Met expression profiles and prognostic significance in esophagogastric adenocarcinoma.

Abstract

e15108 Background: Targeted therapy of HER2 overexpression in patients with esophagogastric adenocarcinoma (EGA) improves survival; however, the effect is transient due to the development of resistance. Targeting of EGFR alone in EGA was not active. cMet overexpression is suggested to be a possible resistance pathway for EGFR and HER-2 inhibition. We characterized the expression profile of the EGFR family of receptors and cMet as well as their prognostic significance in EGA. Methods: This retrospective analysis included all patients (pts) with EGA who underwent primary resection at the University of Florida from 2001 to 2011 without neoadjuvant therapy. Demographics, risk factors, tumor features, and outcome data were analyzed. Central blinded immunohistochemistry (IHC) was performed on paraffin embedded tumor specimens with EGFR, HER2, HER3, HER4 and cMet expression scored as low (0, 1+) or high expression (2+, 3+). Descriptive statistics, Fisher exact test, Cox regression and Kaplan-Meier methods were used for statistical analyses. Results: 52 pts (42 M/10 F) were analyzed with median age 66 years (37-83). Most tumors (58%) were stage I (T1N0). Receptors expression profiles and their associations are presented in the Table. High HER3-HER4 co-expression was found in 35% of cases (p = 0.002). Univariate analysis did not show significant correlation of age, tumor differentiation, BMI, tobacco use and receptor expression with survival. Stage was the only variable that correlated significantly with survival (p=0.02). Conclusions: This is the first study to our knowledge examining the EGFR family expression relationships and cMet in treatment naïve resected EGA tumors. Associations between receptor expression patterns are of clinical interest for rational development of multi-targeted inhibition. Although our data do not significantly show receptor status as a prognostic factor, some receptor expression associations suggest trends towards worse survival. Larger studies are warranted for further investigation. [Table: see text]