Epidermal Growth Factor Receptor Signaling Pathway is Frequently Altered in Ampullary Carcinoma at Protein and Genetic Levels

Our objective was to explore alteration of the epidermal growth factor receptor signaling pathway in ampullary carcinoma. Immunohistochemical studies were employed to evaluate expression of amphiregulin as well as expression and activation of epidermal growth factor receptor. A lab developed assay was used to identify mutations in the epidermal growth factor receptor pathway genes, including KRAS, BRAF, PIK3CA, PTEN and AKT1. Fifty two ampullary carcinomas were identified, including 25 intestinal-type and 24 pancreatobiliary-type tumors with the intestinal type being associated with a younger age at diagnosis (p=0.03) and a better prognosis (p<0.01). Expression of amphiregulin correlated the better differentiation (p<0.01), but no difference was observed between two major histologic types. Expression and activation of epidermal growth factor receptor was more commonly seen in the pancreatobiliary type (p<0.01). Mutations were detected in 50% of the pancreatobiliary type and 60% of the intestinal type. KRAS was the most common gene mutated in the pancreatobiliary type (42%) as well as the intestinal type (52%). Other mutations detected included PIK3CA, and SMAD4 and BRAF. KRAS mutations at codons 12 and 13 did not impact adversely on overall survival. In conclusion, epidermal growth factor receptor expression and activation were different between intestinal- and pancreatobiliary-type ampullary carcinoma. KRAS mutation was common in both histologic types; however, the incidence appeared to be lower in the pancreatobiliary type compared to its pancreatic counterpart, pancreatic ductal adenocarcinoma. Mutational analysis of the epidermal growth factor receptor pathway genes may provide important insights into personalized treatment for patients with ampullary carcinoma.