Circulating soluble Fas concentration in breast cancer patients

Fas/Fas ligand (FasL) system, a major regulator of apoptosis, is involved i n cancer cell death induced by the immune system and anticancer drugs. Fas is a cell-surface receptor that exists in two forms, transmembrane and solu ble. The former induces apoptosis by ligation of Fast or agonistic anti-Fas antibody, whereas the latter inhibits Fas-mediated apoptosis by neutralizi ng its ligand. In this study, we examined circulating soluble Fas (sFas) co ncentration in 118 healthy people, 162 primary and 71 recurrent breast canc er patients by ELISA. In the healthy group, men showed higher sFas concentr ations than women (P < 0.001), In both sexes, sFas levels increased with ag e, and the age-matched cutoff value was determined. The median sFas concent ration in primary and recurrent cancer patients was 0.815 and 1.510 ng/ml, both of which were higher than in normal female controls (0.580 ng/ml; P = 0.024 and P < 0.001, respectively). Among primary cancer patients, although no significant correlation was found between sFas concentration and clinic al parameters other than menopausal status, high-sFas patients had a worse prognosis than low-sFas patients for both overall and disease-free survival (P = 0.013 and P = 0.032, respectively). The multivariate analysis confirm ed that circulating sFas concentration was an independent prognostic indica tor (P = 0.020 for overall survival, P = 0.025 for disease-free survival). We looked at the recurrent cancer patients, and sFas levels were higher in patients with liver metastasis compared with those with other recurrent sit es (P = 0.010), and high-sFas patients showed a worse prognosis than low-sF as patients (P = 0.037), Our data demonstrate that, compared with healthy f emale controls, breast cancer patients, especially those with liver metasta ses, have higher circulating sFas levels. sFas may be useful once these res ults are confirmed by larger studies.