Serum soluble Fas level as a prognostic factor in patients with gynecological malignancies

The Fas-Fas ligand system is important in apoptosis mediated by CTLs and na tural killer cells. The suppression of apoptosis contributes to carcinogene sis, as well as to a resistance to chemotherapy and radiotherapy. Circulati ng soluble Fas (sFas), which is generated by alternative mRNA splicing, can antagonize cell-surface Fas function. We investigated sFas levels in 64 pa tients with gynecological malignancies (28 cervical carcinomas, 18 endometr ial carcinomas, and 18 ovarian carcinomas) and in 24 healthy female donors by using a Fas-specific ELISA, In each carcinoma group, serum sFas demonstr ated a statistically significant elevation relative to levels in normal con trols (P < 0.0001). Levels of serum sFas in patients with advanced cancer ( FIGO stages III and IV) significantly exceeded those in patients with local ized cancer (FIGO stages I and II) or those in normal control subjects (P < 0.0001). We divided the patients into two groups based on the level of ser um sFas and examined the relationship between serum sFas levels and surviva l. No deaths occurred in the groups with cervical and endometrial cancer wi th a serum sFas level <1.5 ng/ml, Survival rates in groups with cervical ca rcinoma, endometrial carcinoma, and ovarian carcinoma with a serum sFas lev el <1.5 ng/ml exceeded those in groups with sFas levels of greater than or equal to 1.5 ng/ml (P < 0.001, P = 0.128, and P = 0.012, respectively). Pro portional hazard models demonstrated that serum sFas level was a statistica lly significant factor (P = 0.0196) for survival, as well as histological g rade (P = 0.0168) in ovarian carcinoma.