Expression of Fas/Fas ligand (FasL) and its involvement in infiltrating lymphocytes in hepatocellular carcinoma (HCC)

Background. This study was conducted to examine the expression of Fas/Fas l igand (FasL), to elucidate its relationship with tumor-infiltrating lymphoc ytes (TILs), and to detect possible gene mutation of Fas/FasL in patients w ith hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC). Methods . Indirect immunohistochemical staining was performed on formalin-fixed, pa raffin-embedded sections of liver biopsy and surgery specimens from five no rmal livers, and from the livers of 30 patients with HCC. Fas/FasL mRNA-exp ressing cells and apoptotic cells were detected by in situ hybridization an d DNA nick end labeling (TUNEL), respectively. We also performed polymerase chain reaction (PCR) -amplifying and direct sequencing for the Fas/FasL ge ne. Results. Fas/FasL and its mRNA were localized on the, membrane or in th e cytoplasm in some HCC cells, as well as hepatocytes. Their expression was enhanced in areas with infiltrating inflammatory cells in the noncancerous regions of liver tissue and on the margins of the cancerous tissue. The po sitivity rate for TUNEL was elevated along these margins. The labeling inde x of Fas/FasL was lower in the cancerous liver tissue than in the surroundi ng noncancerous region (P < 0.01), and tended to decrease in proportion to the malignancy of tumor cells; Fas/FasL expression was not found on poorly differentiated type cancer cells. Fas(-)/FasL(+), FasL-mRNA(+) HCC cells we re seen in one specimen of moderately differentiated type. Some CD8+T lymph ocytes were TUNEL-positive around the cancerous region. In this study, canc erous and noncancerous tissues in HCC revealed no genetic mutations in any exons of Fas/FasL. Conclusions. These findings suggest that Fas/FasL expres sion was decreased in proportion to the malignancy of tumor cells, and that infiltrating CD8+T lymphocytes play a role in apoptosis in HCC. The apopto sis in HCC could be regulated by the suppression of Fas/FasL expression, or , sometimes, by the enhancement of FasL expression.