Liver cell dysplasia: reactivities for c-met protein, Rb protein, E-cadherin and transforming growth factor-beta 1 in comparison with hepatocellular carcinoma.

In the present retrospective study, liver cell dysplasia (LCD) occurring in cirrhotic livers associated or not associated with hepatocellular carcinoma (HCC) was immunohistochemically analyzed for the expression of hepatocyte growth factor receptor (c-met protein), Rb (retinoblastoma gene) protein, E-cadherin, and transforming growth factor-beta-1 (TGF-beta-1). Cytoplasmic c-met protein staining was observed in about half of the HCC's, and its prevalence was about twice as high in high grade vs. low grade tumors, but it was not correlated with proliferative activity as based on PCNA labelling. In LCD, reactivity for c-met protein was restricted to the small cell type. Nuclear staining for Rb protein was found in HCC's, and was not related to type, grade or proliferative activity, whereas no immunoreactivity was observed in normal, hyperplastic or dysplastic hepatocytes. Expression of E-cadherin prevailed in HCC's of lower grade, and particularly in those with a trabecular or acinar growth pattern. E-cadherin staining was detectable in normal and large dysplastic hepatocytes, but not in small dysplastic liver cells. TGF-beta-1 reactivity was observed in more than half the HCC's, but not in normal or dysplastic hepatocytes. These findings underline the phenotypic difference between large cell and small cell liver dysplasia, and support the hypothesis that small cell dysplasia is a precursor lesion in a hepatocarcinogenic pathway.