Expression relationships among EGFR family members and c-Met in esophagogastric adenocarcinoma.

Abstract

75 Background: The incidence of esophagogastric adenocarcinoma is on the rise. The only targeted therapy that improves patient outcomes is the anti-HER2 antibody, trastuzumab; however, benefit is limited to cases with HER2 overexpression. Inhibition of EGFR in EGA is unsuccessful. cMet overexpression is a proposed resistance pathway for EGFR family inhibition. We sought to characterize the co-expression relationships among the EGFR family and cMet to identify potential dual therapeutic targets. Methods: This study included all sequential patients (pts) with adenocarcinoma of the esophagus and GEJ who underwent primary resection between 2001 to 2011 without neoadjuvant therapy or HER2 inhibition. Demographics, risk factors, tumor features, and outcome data were analyzed. Central blinded immunohistochemistry (IHC) was performed on FFPE tumor specimens with EGFR, HER2, HER3, HER4 and cMet expression scored as low/negative or high/positive expression. Descriptive statistics, Exact chi square test and Cox regression model were used for statistical analyses. Results: 48 pts (39 M/9 F) were eligible (median age 66yr; 37-83). Most (63%) were stage I (T1N0) and 93% had underlying Barrett’s esophagus. High expression of EGFR, HER2, HER3, HER4 and cMet were present in 70%, 43%, 77%, 38% and 56% of tumors respectively. HER3 and HER4 were commonly co-expressed (p=0.003) and moderately differentiated tumors had high expression of HER3 (p=0.01). Stage was the only variable that correlated significantly with survival (p=0.007). Conclusions: This study demonstrated that static baseline cMET expression levels are not associated with EGFR family expression profiles, although HER3/HER4 co-expression is common. No receptors demonstrated prognostic value. Further investigation into dynamic cMET expression changes related to active EGFR inhibition including prognostic and predictive value is warranted.