Immunohistochemical study of expression of p-glycoprotein and mutant p53 protein in hepatocellular carcinoma from the viewpoint of modulation of transcriptional activity of MDR1 gene

Abstract

Recently, it was reported that the promoter region of the human MDR1 gene was a target for the p53 tumor suppressor gene product; a mutant p53 specifically stimulated the MDR1 gene promoter. To elucidate how both proteins, p-glycoprotein and mutant p53 protein, correlate with each other in a human carcinoma cell of HCC in vivo, the expression of these proteins was investigated immunohistochemically. The results from 42 cases of HCC revealed that 28 cases (66.7%) had p-glycoprotein and 12 cases (28.6%) had mutant p53 protein. Regarding the positivity rate of each protein in each histologic differentiation, that of p-glycoprotein was higher in well or moderately differentiated grade than in poorly differentiated grade, whereas that of mutant p53 protein was lower in well or moderately differentiated grade. The distribution of each protein-positive cell was not always uniform through the tumor sections, and the locations of p-glycoprotein-positive carcinoma cells and mutant p53 protein-positive carcinoma cells were poorly coincident in the serial sections of the same case. It seems that p53 protein may not directly affect the expression of p-glycoprotein, therefore p-glycoprotein overexpression in HCC could not be explained only by the direct correlation between mutational inactivation of p53 and stimulation of transcriptional activity of MDR1 gene.