Prognostic Significance of EGFR, HER2, and c-Met Overexpression in Surgically Treated Patients with Adenocarcinoma of the Ampulla of Vater.

Simple Summary: Adenocarcinoma of the ampulla of Vater (AAC) is a rare cancer that arises from various histologic subtypes, creating a diverse group of tumors in need of new therapeutic strategies. This study examines the expression of epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2 (HER2), and c-Met in AAC to explore their potential as druggable targets. Among 87 patients, EGFR overexpression was found in 87.4%, HER2 in 11.5%, and c-Met in 50%. EGFR overexpression was more common in the pancreatobiliary subtype and linked to a higher histologic grade. EGFR-positive AAC patients had worse disease-free and overall survival compared to EGFR-negative patients. Although HER2-positive AAC showed a trend towards shorter survival, it was not statistically significant. In systemic disease, survival outcomes were unaffected by EGFR, HER2, and c-Met expression, although the HER2-positive group tended towards worse progression-free survival. These results highlight the need for further research to evaluate targeted treatments in AAC patients with these protein expressions. Adenocarcinoma of the ampulla of Vater (AAC) is a rare malignancy with heterogeneous tumors arising from various histologic subtypes, necessitating new therapeutic strategies. This study examines epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2 (HER2), and c-Met expression in AAC, given their potential as druggable targets. Among 87 patients who underwent curative resection, EGFR overexpression was found in 87.4%, HER2 in 11.5%, and c-Met in 50%. EGFR overexpression was more common in the pancreatobiliary subtype (p = 0.018) and associated with a higher histologic grade (p = 0.008). HER2 did not correlate with clinicopathological features, while c-Met was more common in node-negative groups (p = 0.004) and often co-expressed with EGFR (p = 0.049). EGFR-positive patients had worse disease-free (HR = 2.89; 95% CI, 1.35–6.20; p = 0.061) and overall survival (HR = 6.89; 95% CI, 2.94–16.2; p = 0.026) than EGFR-negative patients. HER2-positive AAC showed a trend towards shorter survival, although not statistically significant, and c-Met had no impact on survival outcomes. In the context of systemic disease, survival outcomes did not vary according to EGFR, HER2, and c-Met expression, but the HER2-positive group showed a trend towards inferior progression-free survival (HR = 1.90; 95% CI, 0.56–6.41; p = 0.166). This study underscores the potential of EGFR, HER2, and c-Met as targets for personalized therapy in AAC, warranting further research to evaluate targeted treatments. [ABSTRACT FROM AUTHOR]