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

• Published in: American journal of clinical pathology 2001-09, Vol.116 (3), p.369-376
• Main Authors: MIKAMI, Tetuo, SAEGUSA, Makoto, MITOMI, Hiroyuki, YANAGISAWA, Nobuyuki, ICHINOE, Masaaki, OKAYASU, Isao
• Format: Article
• Language: English
• Subjects: alpha Catenin; beta Catenin; Bile Duct Neoplasms - genetics; Bile Duct Neoplasms - metabolism; Bile Duct Neoplasms - mortality; Bile Duct Neoplasms - pathology; Bile Ducts, Extrahepatic - metabolism; Bile Ducts, Extrahepatic - pathology; Biological and medical sciences; Blotting, Southern; Cadherins - genetics; Cadherins - metabolism; Carcinoma - genetics; Carcinoma - metabolism; Carcinoma - mortality; Carcinoma - secondary; Cell Transformation, Neoplastic; Cytoskeletal Proteins - genetics; Cytoskeletal Proteins - metabolism; Disease-Free Survival; DNA, Neoplasm - analysis; Gastroenterology. Liver. Pancreas. Abdomen; Humans; Hyaluronan Receptors - genetics; Hyaluronan Receptors - metabolism; Immunoenzyme Techniques; Liver. Biliary tract. Portal circulation. Exocrine pancreas; Medical sciences; Mucous Membrane - metabolism; Mucous Membrane - pathology; Oligonucleotide Probes - chemistry; Proportional Hazards Models; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - metabolism; Survival Rate; Trans-Activators; Tumors
• ISSN: 0002-9173
• DOI: 10.1309/VV6D-3GAH-VEJM-DUJT

To clarify the relation between alteration of expression of cell adhesion molecules and progression of extrahepatic bile duct carcinomas. 55 cases were immunohistochemically examined for E-cadherin, alpha-catenin, beta-catenin, and CD44, with additional reverse transcription-polymerase chain reaction and Southern blotting hybridization (RT-PCR/SBH) assays. Levels of E-cadherin, alpha-catenin, and beta-catenin proteins were lower in carcinomas than in normal mucosa, while CD44 variants 3 and 6 were upregulated. Well-differentiated carcinoma showed higher expression of E-cadherin and alpha-catenin than moderately to poorly differentiated types. Macroscopically papillary lesions had higher expression of E-cadherin than their nonpapillary counterparts. RT-PCR/SBH for CD44 revealed the CD44 variant form to be more prevalent in carcinoma than in normal mucosa, correlating with the immunohistochemical results, and with more exon variety. The Cox proportional hazards test identified histologic type and E-cadherin expression as prognostic factors. Among the examined molecules, E-cadherin was especially related to papillary mass formation and a good prognosis.