Pancreatic cancer is a malignant neoplasm with an extremely poor prognosis. The mechanisms of aggressive growth and metastasis are currently not well understood. Expression of epidermal growth factor receptor (EGFR) has been suggested to be associated with the malignant transformation of pancreatic cancer. In this study, we examined the EGFR status of 52 pancreatic tumors by PCR-sequencing (exons 19 and 21), immunohistochemistry and FISH probes. We subsequently investigated the relationship between EGFR status and clinicopathological factors. Somatic alterations in EGFR (R841R, T571T and R831C) were observed only in ductal adenocarcinoma (3/34). In 4 (8%) of the 52 tumors analyzed EGFR was overexpressed, 6 (12%) of the tumors showed moderate expression while 19 (32%) were weakly stained. EGFR overexpression (3+ score) was frequently found in endocrine tumors (29%) followed of ampullary tumors (13%; p<0,01). No significant correlation was observed between the presence of a somatic EGFR mutation and clinicopathological variables. Fluorescence in situ hybridization (FISH) analysis did not demonstrate amplification in any tumors. Only three somatic mutations in the EGFR gene were detected in pancreatic ductal adenocarcinoma and no association was observed with the clinical variables. Our results suggest that EGFR mutations are rare in pancreatic tumors and not associated with clinical prognosis, and treatment response.

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