Expression of Cadherin‐Catenin Cell Adhesion Molecules, Phosphorylated Tyrosine Residues and Growth Factor Receptor‐tyrosine Kinases in Gastric Cancers

Tyrosine phosphorylation of β‐catenin, an intracytoplasmic E‐cadherin‐binding protein, has been shown to disrupt the cadherin‐mediated cell adhesion system in vitro . In order to investigate the relationships of expression and tyrosine phosphorylation of cadherin‐catenin molecules and expression of growth factor receptor‐tyrosine kinase with loose cell‐to‐cell adhesion, immunohistochemical staining for E‐cadherin, α‐ and β‐catenin, phosphorylated tyrosine residues and tyrosine kinase receptors, including c‐erbB‐2 , epidermal growth factor‐receptor (EGF‐R), c‐met and K‐ sam , in 17 undifferentiated‐ and 10 differentiated‐type human gastric cancers was performed. Loss or reduced expressions of E‐cadherin and α‐ and β‐catenin (11, 11, 10 cancers, respectively) were observed in the former, but not the latter. Diffuse cytoplasmic staining of E‐cadherin, α‐ and β‐catenin and phosphotyrosine residues was observed frequently in the undifferentiated‐type cancers. The cytoplasmic localization of phosphotyrosine residues in undifferentiated‐type cancers was correlated significantly with K‐ sam expression ( P <0.01) and diffuse cytoplasmic staining of E‐cadherin ( P <0.05) and β‐catenin ( P <0.05). Expression of K‐sam protein was detected significantly more frequently in undifferentiated‐ (6/17; P <0.05) than differentiated‐type adenocarcinomas whereas the converse applied to c‐erbB‐2 expression (8/10 of the latter, P <0.05). Tyrosine phosphorylation of β‐catenin was directly confirmed in the protein extracts of one undifferentiated‐type gastric cancer. These data indicate that alteration of tyrosine phosphorylation status associated with K‐ sam expression may cause the cytoplasmic distribution of cadherin‐catenin molecules and loose cell‐cell adhesion in undifferentiated‐type gastric cancers.