Increased soluble CD95 (sFas/CD95) serum level correlates with poor prognosis in melanoma patients

Functional impairment of the Fas/CD95 receptor-ligand system is associated with the development and progression of malignancies. One possible cause mi ght be the inhibition of the formation of a functional Fas/CD95-FasL comple x by soluble Fas/CD95 molecules (sFas/CD95), In the present study we determ ined sFas/CD95 serum concentration in 125 melanoma patients of different cl inical stages of disease compared with 30 healthy controls using an ELISA, sFas/CD95 serum level was significantly elevated (P < 0.0005) in melanoma p atients (mean +/- SE = 8.60 +/- 0.26 ng/ml) compared with healthy controls (mean +/- SE = 6.27 +/- 0.25 ng/ml). Univariate analysis revealed a correla tion of sFas/CD95 serum concentration with advanced stages of disease (P = 0.009), Only a slight increase in sFas/CD95 serum level (P = 0.057) could b e observed in regard to the tumor burden. Patients undergoing current treat ment with cytostatics (n = 18) revealed a strong increase in sFas/CD95 seru m level (P < 0.0005), whereas treatment with IFN-alpha alone or combined,vi th cytostatics (n = 19) showed no change in serum sFas/CD95 concentration, According to univariate analysis, elevated sFas/CD95 serum levels were asso ciated with a poor overall (P < 0.005) and a progression-free (P <less than > 0.0005) survival, Multivariate analysis revealed sFas/CD95 serum concentr ation as an independent predictive factor for progression-free (P = 0.011), but not overall (P = 0.078), survival, Our results show a prognostic relev ance of serum sFas/CD95 in melanoma patients, indicating that the evaluatio n of sFas/CD95 serum level may be important for the selection of therapeuti c strategies.