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.
Pichon
Marie-France
MF
Laboratoire d'Oncobiologie, Centre Rend Huguenin de Lutte Contre le Cancer, 92 210 Saint-Cloud, France. mf.pichon@stcloud-huguenin.org
Labroquère
Marc
M
Rezaï
Keyvan
K
Lokiec
François
F
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000493:pharmacokinetics / Q000627:therapeutic use; D002945:Cisplatin / Q000493:pharmacokinetics; D004317:Doxorubicin / Q000493:pharmacokinetics; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000097:blood / Q000276:immunology; D005260:Female; D005472:Fluorouracil / Q000097:blood / Q000493:pharmacokinetics; D006801:Humans; D007069:Ifosfamide / Q000493:pharmacokinetics; D007633:Keratins / Q000097:blood* / Q000276:immunology; D008297:Male; D009369:Neoplasms / Q000097:blood* / Q000188:drug therapy* / Q000276:immunology; D010865:Pilot Projects; D019014:fas Receptor / Q000097:blood*
D000939:Epitopes; D019014:fas Receptor; D007633:Keratins; D004317:Doxorubicin; D002945:Cisplatin; D005472:Fluorouracil; D007069:Ifosfamide