The alteration of Fas receptor and ligand system in hepatocellular carcinomas: How do hepatoma cells escape from the host immune surveillance in vivo?

Escape from the immune surveillance may play an important role in tumor out growth and metastasis. Alteration of the Fas receptor (Fas)/ligand (FasL) s ystem including soluble forms is regarded as one of the mechanisms preventi ng the immune system from rejecting the tumor cells. However, less attentio n has been paid to the role of Fas/FasL interaction in vivo, Therefore, we investigated the expression of Fas and Fast by immunohistochemistry and rev erse-transcription polymerase chain reaction (RT-PCR) and measured the seru m levels of soluble Fas (sFas) and Fast (sFasL) in 44 patients with hepatoc ellular carcinoma (HCC). In the noncancerous liver tissues, Fas expression was up-regulated in most cases, and Fast expression was detected in 6 cases . In Fas-positive HCC cases (n = 15), the intrahepatic metastatic foci was less (P =.037), apoptosis of tumor cells was more (P =.004), the disease-fr ee survival rate was higher (P =.004), and p53-positive cases were less (P =.003), compared with Fas-negative cases. The sFas and sFasL levels in HCC patients were significantly higher and lower than those in controls, respec tively. RT-PCR and immunohistochemistry revealed generation of sFas in the hepatocytes and tumor-infiltrating mononuclear cells rather than in hepatom a cells. Accordingly, hepatoma cells may eliminate Fas expression on themse lves and let the hepatocytes and infiltrating mononuclear cells generate sF as to escape from the immune system and to produce metastasis. Fast might c ontribute to malignant transformation in some circumstances, because hepato cytes in the pericancerous pseudolobules expressed FasL.