Alteration of adhesion molecule expression and cellular polarity in hepatocellular carcinoma

Aims: To study the expression of adhesion molecules in human liver and their possible roles during hepatocarcinogenesis. Methods and results: The expression of adhesion molecules in normal liver tissues, benign including probable premalignant lesions and malignant lesions was systematically investigated by immunohistochemistry and Western blotting. In normal liver, both hepatocytes and bile duct cells expressed symplekin, desmoglein 1/2, desmocollin 2, desmoplakin and plakophilin 2, but did not express desmocollin 1/3 or plakophilin 1. In benign hepatocyte lesions, expression of the adherens junctions and desmosomes was uniform and slightly increased, but symplekin appeared to show reduced expression in dysplastic lesions. In hepatocellular carcinoma (HCC), the expression of adhesion molecules was often heterogeneous and of abnormal location. Tumour cells with an abnormal distribution or loss of adhesion molecules showed an apolar arrangement of tissue architecture. The expression levels of the adhesion molecules correlated with the differentiation grades of HCC cells. Conclusions: The decreased expression of symplekin may be an early step in the transformation of hepatocytes, whereas alteration of the expression of adherens junctions and desmosomes may indicate more serious changes.