APOPTOSIS AND PROLIFERATION OF HUMAN HEPATOCELLULAR-CARCINOMA

To investigate the contribution of apoptosis, a major mechanism of cel l death, in the growth of hepatocellular carcinoma, we analyzed both a poptosis and cell proliferation in human hepatocellular carcinoma. We used the terminal deoxynucleotidyl transferase-mediated dUTP-biotin ni ck end labeling method and proliferative cell nuclear antigen staining , respectively. Among 21 hepatocellular carcinoma specimens examined, four were well, ten were moderately, and seven were poorly differentia ted hepatocellular carcinoma. Terminal deoxynucleotidyl transferase-me diated dUTP-biotin nick end labeling-positive cells in hepatocellular carcinoma were scattered individually or were sometimes clustered in t he tumors. The terminal deoxynucleotidyl transferase-mediated dUTP-bio tin nick end labeling indices were 0.35+/-0.09, 0.81+/-0.29, and 1.9+/ -0.94 in well, moderately, and poorly differentiated hepatocellular ca rcinoma, respectively. The proliferative cell nuclear antigen labeling indices were 6.6+/-0.9, 13.1+/-3.5, and 26.7+/-6.3 in hepatocellular carcinoma in the same respective order of differentiation. The differe nces in both terminal deoxynucleotidyl transferase-mediated dUTP-bioti n nick end labelling indices and proliferative cell nuclear antigen la beling indices (p<0.05) were significant between well, moderately and poorly differentiated hepatocellular carcinoma. There was a positive c orrelation between the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling and proliferative cell nuclear antigen l abeling indices in hepatocellular carcinoma (r=0.84, p<0.001). This st udy showed that the proliferation rate and the incidence of apoptosis increased as the differentiation grade of hepatocellular carcinoma was lowered, suggesting a rapid turnover of cancer cells in the lower dif ferentiation grades. Apoptosis may thus play an important role in the growth of hepatocellular carcinoma.