E-cadherin, alpha-catenin and beta-catenin in biliary atresia: correlation with apoptosis and cell cycle.

Biliary atresia (BA) is the most common cause of obstructive jaundice in infancy. Although the etiology of BA remains unknown, the ductal plate malformation has been considered to play an important role in the development of BA. Cell-cell adhesion has long been recognized as one of the most important processes in organogenesis. E-cadherin is involved in cell-cell adhesion, together with the catenins. Abnormalities of E-cadherin and associated catenins have not been examined in detail in the liver with BA. We therefore examined immunolocalization of E-cadherin and alpha- and beta-catenins in the BA liver (n = 45) and compared the findings with those in non-BA (n = 11) and fetal liver (n = 21). We semiquantitatively evaluated the findings using H score, which were generated according to the percentage of immunopositive cells and their immunointensity. We also examined mRNA localization of E-cadherin using mRNA in situ hybridization. We then studied the correlation of E-cadherin immunoreactivity with apoptotic cells, and cyclin-dependent kinase inhibitor p27Kip1 immunolocalization of bile duct cells in BA liver (n = 10) and fetal liver (n = 10). In fetal liver, H score of E-cadherin, but not of alpha- and beta-catenins, was significantly lower in the remodeling stage than in the ductal plate (P = 0.0034) and remodeled stages (P = 0.0024). In addition, the H score of E-cadherin, but not alpha- and beta-catenin, in bile duct cells was significantly lower in BA liver than in non-BA liver (P = 0.0132). E-cadherin mRNA hybridization signals were relatively conserved in bile duct cells of BA liver, but decreased in remodeling ductal plate cells of fetal liver. An inverse correlation was detected between the H score of E-cadherin and the TUNEL labeling index (LI) in both fetal and BA liver. In contrast, a positive correlation was detected between the H score of E-cadherin and p27 LI in both fetal and BA liver. These findings suggest that impaired expression of E-cadherin in bile ducts may play an important role in the biological features of BA, possibly associated with cell cycle and apoptosis.