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 exist ence 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 reg eneration and hepatocarcinogenesis, we investigated a possible correlation between human putative progenitor cells and different types of dysplastic f oci. Methods: We determined the immunohistochemical phenotype of dysplastic foci found in 20 cirrhotic liver explants of various etiology, using specific a ntibodies against hepatocyte-type cytokeratin (CK) 8 and CK18, bile duct-ty pe 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 tha t of surrounding parenchyma, Oncocytic foci showed a strong cytoplasmic sta ining 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 an d stained more intensely for CK8 than surrounding hepatocytes. Pour 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 strong er 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 dysplasi a consist of small cells with the same immunohistochemical phenotype as put ative progenitor cells and intermediate hepatocyte-like cells, suggesting t hat differentiating putative progenitor cells can give rise to foci of smal l cell dysplasia.