Inverse relationship between P-glycoprotein expression and its proliferative activity in hepatocellular carcinoma

Hepatocellular carcinomas (HCCs) from 31 patients, cirrhotic livers from 7 patients and normal liver from 8 patients were immunohistochemically assessed in frozen sections using anti-P-glycoprotein (Pgp) monoclonal antibody C219. Immunohistochemical staining with anti-Ki-67 monoclonal antibody MIB-1 was performed for 22 HCCs to assess proliferative activity. Tumor tissues expressed Pgp on the biliary surface and on the luminal surface of cancer cells, which was less extensive than in normal and cirrhotic liver hepatocytes. Expression of Pgp was closely associated with the degree of histological differentiation and the histological type of HCC. Labeling indices (LI) of Pgp expression were 0.68 +/- 0.06 (mean +/- SD) in well, 0.51 +/- 0.14 in moderately and 0.04 +/- 0.06 in poorly differentiated HCC (significant differences among the three groups). LI of Pgp expression in the trabecular (0.55 +/- 0.15) and in the pseudoglandular types (0.44 +/- 0.10) were remarkably higher than in the compact type (0.04 +/- 0.06). The extent of Pgp expression in HCC was significantly inversely related to the extent of Ki-67 expression, in which Pgp expression decreased in highly proliferating tumors. In conclusion, Pgp expression in HCC was clearly related to its proliferative activity.