TENASCIN AND TYPE-IV COLLAGEN EXPRESSION IN LIVER-CELL DYSPLASIA AND IN HEPATOCELLULAR-CARCINOMA

The extracellular matrix (ECM) located in and around tumors is differe nt from normal organ stroma, and there is evidence that it is critical ly involved in carcinogenesis and malignant growth. Whereas an abnorma l composition of ECM in hepatocellular carcinomas (HCC's) has previous ly been demonstrated, not much is known so far with respect to putativ e HCC precursor lesions. We have, therefore, systematically analyzed t he immunohistochemical reactivity for two major ECM components, tenasc in and type IV collagen, in three types of liver cell dysplasia (LCD), and compared the findings with patterns observed in HCC's of differen t types and grades. Tenascin reactivity was generally stronger in HCC' s than in cirrhosis. In cirrhotic nodules harboring areas of LCD, tena scin expression was significantly lower in small cell LCD than in larg e cell LCD. Type IV collagen reactivity in and around HCC's decreased as a function of a lower differentiation grade. In both groups of cirr hosis, i.e. with or without HCC, cirrhotic nodules occupied by the sma ll cell variant of LCD exhibited a significantly lower type IV collage n reactivity than those with large cell LCD or simple regenerative cel ls. Taken together these findings suggest that, similar to adenomatous hyperplasia, small cell LCD is characterized by an abnormal tenascin and type IV collagen expression, thus reflecting the defective ECM pat tern observed in HCC's.