The Fas system is not significantly involved in apoptosis in human hepatocellular carcinoma

We investigated the role of apoptosis in relation to proliferative activity in hepatocellular carcinoma (HCC) using in situ DNA nick end labeling (ISNEL) and immunostaining for the Ki-67 antigen in 35 patients with HCC. We also performed immunostaining for Fas and Fas ligand (Fas L) to determine the relationship between the Fas system and apoptosis. The ratio of the ISNEL labeling index (LI) to the Ki-67 LI was significantly lower in HCC than in surrounding nontumorous liver tissue (p<0.0001), suggesting that a decrease in apoptosis relative to cell proliferation is important in the pathogenesis of HCC. Fas and Fas L were expressed in both HCC and nontumorous tissue, but Fas and Fas L LIs were significantly lower in HCC (p<0.0001). Fas expression by cells near ISNEL-positive cells tended to be increased in nontumorous tissue in mirror-image sections, suggesting that apoptosis is related to Fas expression. However, this pattern was rarely observed in HCC. These findings indicate that the Fas system may not play a major role in apoptosis in HCC.