Expression of P-glycoprotein in hepatocellular carcinoma: A determinant of chemotherapy response

Abstract

To characterize the P-glycoprotein (Pgp) expression in human hepatocellular carcinoma (HCC), we studied 101 cases of HCC treated with surgical resection without prior treatment. Pgp expression was detected immunohistochemically using 2 monoclonal antibodies (C494, C219) and correlated with pathologic features, survival, and p53 expression. Chemotherapy response was analyzed in a separate group of patients with inoperable HCC treated with systemic chemotherapy. Positive immunostaining was seen in 92% and 80% of the tumors with C494 and C219, respectively; bile canalicular type staining was seen in all positive tumors. Pgp expression was less extensive in the tumors than in the corresponding nontumorous liver tissue. Tumor Pgp expression with either antibody had no association with cellular differentiation, aggressive pathologic features, survival, or p53 overexpression. In patients with inoperable HCC, the chemotherapy response was significantly inversely related to Pgp expression with C494 and C219. Pgp was expressed in human HCC but was patchy and less extensive than in the nontumorous tissue. Response to systemic chemotherapy was inversely related to the level of Pgp expression in patients with inoperable tumors. Pgp expression in tumors not treated with chemotherapy was not associated with a more aggressive tumor phenotype or p53 overexpression and did not influence survival.