Overexpression of P-glycoprotein in adenomatous hyperplasia of human liver with cirrhosis.

Adenomatous hyperplasia in the human liver with cirrhosis is similar to the hyperplastic nodule in rat hepato-carcinogenesis in that the mdr gene or its product P-glycoprotein is overexpressed. We immunohistochemically stained archival formalin-fixed, paraffin-embedded sections of 15 adenomatous hyperplasias with or without hepatocellular carcinoma in livers with cirrhosis, using the avidin-biotin-complex method and the JSB-1 monoclonal antibody which specifically binds the cytoplasmic epitope of P-glycoprotein. Of 15 cases with adenomatous hyperplasia, four were found solely in livers with cirrhosis. In six cases, adenomatous hyperplasia and hepatocellular carcinoma were found in the same liver separately. Hepatocellular carcinoma was discovered within adenomatous hyperplasia in five cases. All 15 livers with cirrhosis and those with adenomatous hyperplasia were positively stained for P-glycoprotein. When the grade of staining was compared between adenomatous hyperplasia and the surrounding liver, P-glycoprotein was overexpressed in 12 of 15 cases with adenomatous hyperplasia. P-glycoprotein was also stained more strongly in well-differentiated hepatocellular carcinoma than in the liver, but the staining grade of hepatocellular carcinoma was weaker than that of adenomatous hyperplasia. Moreover, the glycoprotein expression was less when the tumor was less differentiated.