Significant correlations of E-cadherin, catenin, and CD44 variant form expression with carcinoma cell differentiation and prognosis of extrahepatic bile duct carcinomas

To clarify the relation between alteration of expression of cell adhesion m olecules and progression of extrahepatic bile duct carcinomas, 55 cases wer e immunohistochemically examined for E-cadherin, alpha-catenin, beta-cateni n, and CD44, with additional reverse transcription-polymerase chain reactio n and Southern blotting hybridization (RT-PCR/SBH) assays. Levels of E-cadh erin, alpha-catenin, and beta-catenin proteins were lower in carcinomas tha n in normal mucosa, while CD44 variants 3 and 6 were upregulated. Well-diff erentiated carcinoma showed higher expression of E-cadherin and alpha-caten in than moderately to poorly differentiated types. Macroscopically, papilla ry lesions had higher expression of E-cadherin than their nonpapillary coun terparts. RT-PCR/SBH for CD44 revealed the CD44 variant form to be more pre valent in carcinoma than in normal mucosa, correlating with the immunohisto chemical results, and with more exon variety. The Cox proportional hazards test identified histologic type and E-cadherin expression as prognostic fac tors. Among the examined molecules, E-cadherin was especially related to pa pillary mass formation anti a good prognosis.