Prognostic significance of soluble Fas in the serum of patients with bladder cancer

Abstract

Purpose: The interaction of Fas antigen (Fas) and Fas ligand plays an important role in cytotoxic T lymphocyte- and natural killer cell-mediated cytotoxicity against cancer cells. Circulating soluble Fas (sFas) antagonizes cell-surface Fas function and may interfere with immune surveillance against autologous tumors. This possibility was examined in patients with bladder cancer.

Materials and methods: The levels of sFas in the serum of 173 patients with bladder cancer were determined by using an enzyme-linked immunosorbent assay. Cytotoxicity of anti-Fas monoclonal antibody was examined by a 1-day microculture tetrazolium dye assay. Anti-autologous tumor cytotoxic activity was determined by the 12-hour 51Cr release assay.

Results: The mean serum level of sFas in patients with bladder cancer was threefold higher than the mean in normal donors. The patients were divided into 2 groups based on the level of sFas in the serum. Bladder cancer patients with low level of serum sFas (less than the mean value) had a higher disease-specific survival rate, when compared with those with high level of serum sFas (greater than the mean value) in the 5-year followup. There were no statistical differences in patients' age and sex, as well as histological stage and grade of bladder cancer between the patients with high and low levels of serum sFas. Furthermore, patients with Ta bladder cancer with a low level of serum sFas had a longer postoperative tumor-free interval than those with high level in the 5-year followup. Cytotoxic activity of peripheral blood lymphocytes against autologous tumor cells was examined in 25 patients. There was an inverse correlation between the level of serum sFas and anti-autologous tumor cytotoxicity.

Conclusions: The findings suggest that elevated levels of sFas in the serum might be associated with poor prognosis in patients with bladder cancer.