IMMUNOHISTOCHEMICAL STUDY OF EXPRESSION OF P-GLYCOPROTEIN AND MUTANT P53 PROTEIN IN HEPATOCELLULAR-CARCINOMA FROM THE VIEWPOINT OF MODULATION OF TRANSCRIPTIONAL ACTIVITY OF MDR1

Recently, it was reported that the promoter region of the human MDR1 g ene was a target for the p53 tumor suppressor gene product; a mutant p 53 specifically stimulated the MDR1 gene promoter. To elucidate how bo th proteins, p-glycoprotein and mutant p53 protein, correlate with eac h other in a human carcinoma cell of HCC in vivo, the expression of th ese 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-glycopr otein was higher in well or moderately differentiated grade than in po orly differentiated grade, whereas that of mutant p53 protein was lowe r in well or moderately differentiated grade. The distribution of each protein-positive cell was not always uniform through the tumor sectio ns: and the locations of p-glycoprotein-positive carcinoma cells and m utant p53 protein-positive carcinoma cells were poorly coincident in t he serial sections of the same case. It seems that p53 protein may not directly affect the expression of p-glycoprotein, therefore p-glycopr otein 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.