EGFR and HER2 expression and dimerization in esophageal cancer*

Receptor tyrosine kinases (EGFR, HER2) are therapeutic targets in epithelial tumors, whose distinct EGFR/HER2 expression and/or dimerization may affect therapeutic responses. Here, we examined EGFR and HER2 protein expression and dimerization in esophageal squamous cell carcinoma (ESCC) and Barrett’s adenocarcinoma (BAC).

In tissue specimens, HER2 was overexpressed in 18/61 (30%) BACs and 1/49 (2%) ESCCs (p<0.001). In double immunofluorescence (6 cases), intratumoral heterogeneity of EGFR and HER2 expression was observed without major colocalization of HER2 and EGFR. In cell lines^#, preferential EGFR expression was seen in OE21 (ESCC) and HER2 expression in OE33 (BAC) cells by dIF. However, colocalization of EGFR and HER2 occured, especially in OE33 cells. Accordingly, more EGFR/HER2 signals were seen in OE33 than OE21 cells by proximity ligation assay. Normal EPC-hTERT cells showed only marginal EGFR and HER2 expression.

Thus, BAC tissue specimens preferentially express HER2. This is reflected in vitro (OE33), showing dimerization of HER2 with EGFR. In contrast, ESCC tissue specimens have preferential EGFR expression. This is also seen in vitro (OE21), but here EGFR does not readily dimerize with HER2. Distinct EGFR and HER2 hetero- or homodimers may differentially regulate down-stream signalling events, influence BAC and ESCC tumor progression and cellular responses to EGFR/HER2 targeted therapy.