Expression of E-cadherin, α-catenin, β-catenin, and CD44 (standard and variant isoforms) in human cholangiocarcinoma: An immunohistochemical study

Immunolocalization of E-cadherin (E-cad), α-catenin, β-catenin, and CD44 has rarely been investigated in human cholangiocarcinoma (CC). We, therefore, immunohistochemically examined the expression of E-cad, α- catenin, β-catenin, CD44 standard (CD44s), and CD44 variants (CD44v) including CD44v5, CD44v6, CD44v7-8, and CD44v10 in normal adult livers and in 47 cases of CC; and the results were then correlated with tumor grade, vascular invasion, metastasis, p53 expression, proliferative fraction (Ki-67 labeling), and c-erbB2 expression. In normal livers, E-cad, α-catenin and β-catenin, but not CD44s, CD44v5, CD44v6, CD44v7-8, and Cd44v10, were expressed at the cell membrane of normal intrahepatic bile ducts. In CC, membranous expression of E-cad, α-catenin, and β-catenin was the same or reduced when compared with non-cancerous bile ducts in the majority of CC. We found that the down-regulation of E-cad, α-catenin, and β-catenin expression significantly correlated with tumor high grade, but not with vascular invasion, metastasis, p53 expression, Ki-67 labeling, or c-erbB2 expression, except for β-catenin, the down-regulation. CD44s, CD44v5, CD44v6, CD44v7-8 and CD44v10 were frequently expressed at the membrane of CC cells. There were, however, no significant correlations between these aberrant CD44 expression and tumor grade, metastasis, vascular invasion, p53 expression, Ki-67 labeling, or c-erbB2 expression, with a few exceptions of CD44s and CD44v5. We found that CD44s aberrant expression significantly correlated with absence of metastasis and vascular invasion, and that CD44v5 aberrant expression significantly correlated with p53 under-expression. These results suggest that membranous expression of E-cad, α-catenin, and β- catenin is reduced in a majority of CC and this down-regulation correlates with CC high grade, and that β-catenin down-regulation is associated with c- erbB2 down-regulation. The data also suggested that CD44s, CD44v5, CD44v6, CD44v7-8, and CD44v10 may be neoexpressed during carcinogenesis of CC but this neoexpression does not correlate with tumor progression in CC, with the exception of CD44s and Cd44v5.