Variations of soluble fas and cytokeratin 18-Asp 396 neo-epitope in different cancers during chemotherapy

Soluble Fas (sFas) and cytokeratin 18-Asp396 neoepitope (CK18-NE) were measured by ELISA in serial samples from 42 patients with different cancers under chemotherapy and were compared with pharmacokinetic results. Baseline sFas (median 6146 pg/ml, range 3123-16294 pg/ml) was higher in cancer patients than in normal subjects (median 4954 pglml, range 2595-10565 pg/ml, n =95) (p <0.01) and increased with the number of previous chemotherapy lines (p =0.008). During pharmacokinetics, the median sFas response differed significantly with tumour histology (p<0.001) and was correlated to 5-Fluorouracil (rho=0.366, p=0.015, n=45) or cisplatin (rho=0.509, p=0.025, n=21) concentrations but not to anthracyclines or oxazaphosphorine. By Kaplan-Meier analysis, patients with baseline sFas <6146 pg/ml had a longer survival probability (p=0.002). The median baseline CK18-NE did not differ from normal subjects, but its maximum increase differed according to histology (p=0.007) and to drug type (p=0.028). Patients with a maximum increase >67.5% (median) during chemotherapy had a better univariate overall survival (p=0.021). As measured by sFas concentration, chemotherapy induces an anti-apoptotic response of differing intensity according to tumour types and drugs, which has a prognostic value for survival. A CK18-NE elevation, indicative of chemotherapy-induced apoptosis, is linked to good prognosis.