Fas and Fas ligand: strong co-expression in human hepatocytes surrounding hepatocellular carcinoma; can cancer induce suicide in peritumoural cells?

Fas (Apo-1, CD95), a member of the nerve growth factor/tumour necrosis factor receptor superfamily, mediates apoptosis in response to agonistic antibodies or Fas ligand (Fas-L) binding. Fas has been shown to be present on hepatocyte membranes in normal liver and in chronic hepatitis C. At the present time, very limited data are available on the expression of Fas-L. This paper describes a study of 20 cases of active chronic hepatitis of different aetiologies, 20 hepatocellular carcinomas (HCCs) and the adjacent non-tumoural liver parenchyma, and five normal livers. The immunohistochemical expression of Fas and Fas-L was determined using specific monoclonal antibodies. In normal liver, Fas was faintly expressed on membranes of hepatocytes and bile duct cells, while Fas-L was negative. In active chronic hepatitis, Fas expression in hepatocytes was enhanced, resulting in a diffuse honeycomb pattern. Fas-L showed cytoplasmic positivity in hepatocytes in areas of interface hepatitis. Strong expression of Fas as well as Fas-L in the hepatocytes immediately adjacent to HCC was a constant finding. Within the HCCs, Fas-L expression was variable, but present only in a minority of cells. Fas varied from a diffuse honeycomb pattern to focal positivity in occasional cells. There was no correlation between Fas and Fas-L expression in the tumours. In conclusion, hepatocytes can co-express Fas and Fas-L in areas of interface hepatitis and adjacent to HCC, suggesting that they have the ability to induce apoptosis in an autocrine or paracrine way. Within the tumour, the Fas-Fas-L apoptosis pathway seems to be little involved.