Expression of P-glycoprotein in hepatocellular carcinoma: A potential marker of prognosis

Aims-(1) To investigate the immunohistochemical expression of the multidrug resistance gene (MDR1) product P-glycoprotein in histological samples from 31 hepatocellular carcinomas (HCCs); and (2) to correlate the results with cell proliferation, p53 expression, the disease-free interval, and cumulative patient survival. Methods-C219 (a monoclonal antibody), CM-1 (a polyclonal rabbit anti-human antibody) and PC10 (a monoclonal mouse anti-human antibody) were used to detect expression of P-glycoprotein, p53 and proliferating cell nuclear antigen (PCNA), respectively, by means of the avidin-biotin peroxidase method. Results-Membrane bound positivity for P-glycoprotein was observed in 20 (65%) of the 31 HCCs. Cytoplasmic globular positivity was also seen in some cases. There were no significant associations between expression of P-glycoprotein and cell proliferation (determined by PCNA immunoexpression and the mitotic count), or p53 expression. Patients with P-glycoprotein positive tumours had a shorter disease-free interval than those with P-glycoprotein negative tumours, and also had a shorter survival time. There was no difference in survival between P-glycoprotein positive patients who had or had not received chemotherapy suggesting that chemotherapy (mainly mitomycin-C) did not affect survival in these patients. Conclusions-Expression of P-glycoprotein in HCCs is associated with a shorter disease-free interval and shorter survival time. As expression of P-glycoprotein was not associated with cell proliferation or expression of p53, its effect on disease progression and survival seems to be independent of these factors.