IMMUNOHISTOCHEMICAL ANALYSIS OF RETINOBLASTOMA GENE-PRODUCT (PRB) EXPRESSION IN MALIGNANT AND NONMALIGNANT LIVER-DISEASES

The retinoblastoma gene product is a nuclear phosphoprotein that under goes cell cycle-dependent changes in its phosphorylation status. To an alyze the expression of retinoblastoma gene product in the process of liver regeneration and the initiation of hepatocellular carcinoma, we studied immunohistochemically the expression of retinoblastoma gene pr oduct and DNA polymerase alpha (DPA) in 33 patients with various liver diseases. Only a few hepatocytes positive for retinoblastoma gene pro duct were found in undamaged, nonregenerating liver tissues, whereas m any hepatocytes positive for retinoblastoma gene product were detected in specimens of regenerating liver obtained from patients with acute or chronic liver diseases. Similarities were found between distributio n patterns of hepatocytes positive for retinoblastoma gene product and those of hepatocytes positive for DPA, and a highly significant posit ive correlation was found between the number of hepatocyte nuclei stai ned for retinoblastoma gene product per 1000 nuclei examined (R-LI) an d the number of hepatocyte nuclei stained for DPA per 1000 nuclei exam ined (D-LI) in tissues obtained from patients with nonmalignant liver disease. Hepatocellular carcinoma cells positive for DPA were detected in the 14 hepatocellular carcinoma specimens tested. In ten of these specimens, hepatocellular carcinoma cells positive for retinoblastoma gene product were found but not in the other four. For all hepatocellu lar carcinoma specimens, R-LI was proportional to D-LI. Thus in both n onmalignant and malignant liver, retinoblastoma gene product increased in proportion to proliferation of hepatocytes or hepatocellular carci noma cells.