Immunohistochemical study of expression and cellular localization of the multidrug resistance gene product p-glycoprotein in primary liver carcinoma

Abstract

Expression and cellular localization of the multidrug resistance gene product P-glycoprotein, which plays an important role in multidrug resistance to cancer chemotherapy, were immunohistochemically studied in paraffin sections from 55 patients with primary liver carcinoma. Tumor samples from 43 patients with hepatocellular carcinoma (HCC) and from 12 with cholangiocellular carcinoma (CCC) were obtained at autopsy or at surgical resection. Immunohistochemical study was performed by the avidin-biotin-peroxidase technique using monoclonal antibody JSB-1 directed against P-glycoprotein. Anti-P-glycoprotein immunostaining was observed in 67.4% of cases with HCC and in 66.7% of cases with CCC. When P-glycoprotein was detected in HCC, it was localized on the contact surface among tumor cells regardless of histologic type and on the cellular surface facing the blood space in the trabecular type and on the luminal surface in the pseudoglandular type. In CCC, relatively weak immunoreactivity for P-glycoprotein was localized in the cytoplasm of tumor cell both in glandular and nonglandular types, and stronger immunoreactivity was sometimes seen on the luminal surface of glandular type. The incidence of expression of P-glycoprotein was not influenced by previous cancer chemotherapy both in HCC and CCC. In the trabecular type of HCC, however, all cases with P-glycoprotein expression on the cellular surface facing the blood space were from the patients treated with antitumor agents. Resistance to cancer chemotherapy in primary liver carcinoma results from P-glycoprotein protein expression.