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-B-l (TGF-B-l). Cytoplasmic cmet prote in 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 labe lling. In LCD, reactivity for c-met prot e in 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 immunoreac tivity was observed in norma l, hyperplastic or dysplastic he patocytes. Expression of E-c adherin prevailed in I-ICC's of lower grade, and particularly in those with a trabecular or ac inar growth pattern. Ecadherin staining was detectable in normal and large dysplastic hepatocytes, but not in sma ll dysplastic liver cells. TGF-/3-1 reactivity was observed in more than half the I-ICC's, but not in normal or dysplastic hepatocytes.
These findings underline the phenotypic diffe rence between large cell and small cell liver dysplasia, and support the hypothesis that small cell dy spl asia is a precursor lesion in a hepatocarcinogenic pathway
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