Differential Expression of E-Cadherin, beta-Catenin, and S100A4 in Intestinal Type and Nonintestinal Type Ampulla of Vater Cancers

Abstract

Background/Aims: Epithelial-mesenchymal transition (EMT)related proteins may exhibit differential expression in intestinal type or pancreatobiliary type ampulla of Vater carcinomas (AVCs). We evaluated the expression of E-cadherin, beta-catenin, and S100A4 in intestinal and nonintestinal type AVCs and analyzed their relationships with clinicopathological variables and survival. Methods: A clinicopathological review of 105 patients with AVCs and immunohistochemical staining for E-cadherin,beta-catenin, and S100A4 were performed. The association between clinicopathological parameters, histological type, and expression of EMT proteins and their effects on survival were analyzed. Results: Sixty-five intestinal type, 35 pancreatobiliary type, and five other types of AVCs were identified. The severity of EMT changes differed between the AVC types; membranous loss of E-cadherin and beta-catenin was observed in nonintestinal type tumors, whereas aberrant nonmembranous beta-catenin expression was observed in intestinal type tumors. EMT-related changes were more pronounced in the invasive tumor margin than in the tumor center, and these EMT-related changes were related to tumor aggressiveness. Among the clinicopathological parameters, a desmoplastic reaction was related to overall survival, and the reaction was more severe in nonintestinal type than in intestinal type AVCs. Conclusions: Dysregulation of E-cadherin, beta-cadherin, and S100A4 expression may play a role in the carcinogenesis and tumor progression of AVCs.