Prognostic Significance of Serum Soluble Fas Level and Its Change during Regression and Progression of Advanced Prostate Cancer

Abstract

Abstract. To evaluate the clinical usefulness of serum soluble Fas (sFas) and sFas ligand as a prognostic factor and for monitoring the regression and progression of metastatic prostate cancer treated with endocrine therapy, sFas and sFas ligand were measured in sera collected from 30 patients with untreated metastatic prostate cancer. sFas levels were measured sequentially in 16 patients who had progressed to a state of elevated prostate-specific antigen (PSA) and 5 patients who were in regression following endocrine therapy. Serum sFas levels in patients with metastatic prostate cancer were found to be significantly higher than that of control patients with benign prostate hyperplasia. Patients with low levels of serum sFas had a higher cause-specific survival rate and a higher PSA progression-free rate compared with patients with high levels of serum sFas. In patients who suffered PSA progression following endocrine therapy, serum sFas increased in parallel to the increase in PSA levels although the magnitude of change in sFas was very small. In patients whose tumor regressed following therapy, sFas levels did not change. sFas ligand levels were very low or below measurable levels in all specimens. sFas levels might be associated with poor prognosis in metastatic prostate cancer. Serum sFas ligand appears to have limited clinical relevance.

Association between FAS polymorphism and prostate cancer development

“…Membrane Fas receptors trigger apoptosis whereas, on the other hand soluble Fas (sFas), which lacks transmembrane domain, binds to Fas ligand antagonizing Fas-Fas ligand apoptotic pathway. 45,46 Jiang et al 42 have found an elevated expression with a cytoplasmic staining pattern in high-grade prostatic intraepithelial neoplasia and prostatic adenocarcinomas 43,44 Serum sFas is also elevated in bladder cancer and is associated with poor prognosis 47 and predicts early recurrences in patients with Ta bladder cancer. 48 Another study in bladder cancer suggests that sFas is likely to be produced and released by bladder urothelial cell carcinoma cells and that urine sFas levels could be an independent predictor of the presence and invasiveness of bladder cancer.…”

“…9,16,17 However, our results may be in accordance with the recently published studies suggesting the opposite hypothesis. [41][42][43][44] Fas exists as membrane-bound and soluble forms with opposite roles on triggering apoptosis. They derive from the same gene by alternative splicing.…”

The effect of bevacizumab on serum soluble FAS/FASL and TRAIL and its receptors (DR4 and DR5) in metastatic colorectal cancer

“…Elevated sFAS has been reported in serum of patients with colon, prostate, cervix, ovarian, bladder, renal cell, breast and hepatocellular cancers (Furuya et al 2001(Furuya et al , 2003HeXer et al 2000;Konno et al 2000;Mizutani et al 1998;Nonomura et al 2000;Midis et al 1996;Jodo et al 1998). Serum sFAS levels before treatment have been suggested to be a prognostic factor in some tumors (Furuya et al 2003;HeXer et al 2000;Konno et al 2000;Mizutani et al 1998). Elevation of serum sFASL levels was reported in gastric cancer patients (Tsutsumi et al 2000), but it was not detected in prostate cancer (Furuya et al 2003;Perabo et al 2001).…”

“…Failure of this interaction may prolong survival of tumor cells leading to the development and progression of malignancy (Cheng et al 1994). Elevated sFAS has been reported in serum of patients with colon, prostate, cervix, ovarian, bladder, renal cell, breast and hepatocellular cancers (Furuya et al 2001(Furuya et al , 2003HeXer et al 2000;Konno et al 2000;Mizutani et al 1998;Nonomura et al 2000;Midis et al 1996;Jodo et al 1998). Serum sFAS levels before treatment have been suggested to be a prognostic factor in some tumors (Furuya et al 2003;HeXer et al 2000;Konno et al 2000;Mizutani et al 1998).…”

FAP‐1‐mediated activation of NF‐κB induces resistance of head and neck cancer to fas‐induced apoptosis

“…sFas is one of the alternatively spliced variants of Fas which does not have the transmembrane domain and thus is readily secreted [Cheng et al, 1994]. Serum levels of sFas are reported to be higher in cancer patients, including those with SCCHN, than in healthy controls [Knipping et al, 1995;Alecu et al, 2002;Furuya et al, 2003;Pignataro et al, 2003]. Although sFas was detected in culture supernatants of SCCHN cells, its levels did not correlate with the susceptibility of these cells to Fas-induced apoptosis.…”