The immunohistochemical phenotype of dysplastic foci in human liver: correlation with putative progenitor cells.

BACKGROUND/AIMS: In previous studies we found strong evidence for the existence and activation in human liver of putative progenitor cells resembling oval cells in rat liver. In view of the known role of rat oval cells in regeneration and hepatocarcinogenesis, we investigated a possible correlation between human putative progenitor cells and different types of dysplastic foci. METHODS: We determined the immunohistochemical phenotype of dysplastic foci found in 20 cirrhotic liver explants of various etiology, using specific antibodies against hepatocyte-type cytokeratin (CK) 8 and CK18, bile duct-type CK7 and CK19, chromogranin-A (chrom-A) and rat oval cell marker OV-6. RESULTS: All 12 foci of large cell dysplasia had a phenotype similar to that of surrounding parenchyma. Oncocytic foci showed a strong cytoplasmic staining for CK7. Three out of six of these foci contained "progenitor cells", which are small cells immunoreactive for CK18, CK7, CK19, OV-6, chrom-A and stained more intensely for CK8 than surrounding hepatocytes. Four out of eight glycogen-storing foci contained CK7-positive intermediate hepatocyte-like cells and "progenitor cells". Sixteen out of 29 small cell dysplastic foci consisted of "progenitor cells" and intermediate hepatocyte-like cells which were immunoreactive for CK7, CK18, OV-6, chrom-A and showed a stronger cytoplasmic positivity for CK8 than surrounding hepatocytes. CONCLUSIONS: Foci of large cell dysplasia show no correlation with putative progenitor cells. Half of the oncocytic and glycogen-storing foci contain "progenitor cells", while more than half of the foci of small cell dysplasia consist of small cells with the same immunohistochemical phenotype as putative progenitor cells and intermediate hepatocyte-like cells, suggesting that differentiating putative progenitor cells can give rise to foci of small cell dysplasia.