Expression of P-glycoprotein in hepatocellular carcinoma: a potential marker of prognosis.
OBJECTIVE
(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.
Soini
Y
Y
Department of Pathology, University of Oulu, Finland.
Virkajärvi
N
N
Raunio
H
H
Pääkkö
P
P
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000032:analysis* / Q000235:genetics; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000235:genetics; D006528:Carcinoma, Hepatocellular / Q000737:chemistry* / Q000188:drug therapy; D002455:Cell Division / Q000235:genetics; D018572:Disease-Free Survival; D018432:Drug Resistance, Multiple / Q000235:genetics*; D005260:Female; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000737:chemistry* / Q000188:drug therapy; D008297:Male; D016685:Mitomycin / Q000627:therapeutic use; D011379:Prognosis; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D016159:Tumor Suppressor Protein p53 / Q000032:analysis
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D014408:Biomarkers, Tumor; D018809:Proliferating Cell Nuclear Antigen; D016159:Tumor Suppressor Protein p53; D016685:Mitomycin