ORIGINAL ARTICLE Is there any impact of plasma M30 and M65 levels on progression-free survival of patients with advanced gastric cancer? Ahmet Bilici • Bala Basak Oven Ustaalioglu • Serif Ercan • Asuman Orcun • Mesut Seker • Taflan Salepci • Mahmut Gumus Received: 9 August 2010 / Accepted: 27 September 2010 / Published online: 22 October 2010 Ó Springer-Verlag 2010 Abstract Purpose M30 and M65 are different circulating frag- ments of cytokeratin 18. They release during apoptotic cell death, so it is believed that they reflect cell death of epi- thelial tumors. The aim of this study was to determine the prognostic value of plasma M30 and M65 levels in pre- dicting of survival for patients with advanced gastric can- cer compare with healthy controls. Methods Thirty-four patients with advanced gastric can- cer and thirty-two healthy controls were included. Plasma M30 and M65 values were measured by quantitative ELISA method. Results The median age of patients and control groups was 60 and 56 years, respectively. No difference was detected between patient and control groups with respect to plasma median M30 values (390.4 vs. 270.7 U/l, respec- tively, P = 0.10). The median plasma M65 values of patients were significantly higher than those of control group (1232.1 vs. 580.1 U/l, P \ 0.001). The best cut-off values for plasma M30 and M65 for predicting progres- sion-free survival (PFS) were 277.7 and 1434.9 U/l in ROC analysis. The patients whose plasma M30 values were higher than 277.7 U/l had worse PFS than patients with plasma M30 value \ 277.7 U/l (8.9 vs. 11.2, respectively, P = 0.01). The median PFS of patients whose M65 levels lower than or equal to 1434.9 U/l was better than that of patients whose M65 levels were [ 1434.9 U/l (12.4 vs. 10.4, respectively, P = 0.04). But plasma M30 and M65 level in patient group were not found to be an important prognostic factor for PFS in the multivariate analysis. Conclusions These results showed that plasma M65 val- ues were significantly elevated in patients with advanced gastric cancer compared to healthy people. Moreover, both increased plasma M30 and M65 levels can predict PFS in patients with gastric cancer. Keywords Plasma M30 level Á Plasma M65 levels Á Gastric cancer Á Survival Introduction Cytokeratin 18 (CK-18) is a member of the intermediate filament family of cytoskeletal protein and is widely found in epithelial and endothelial cells lining of the respiratory and gastrointestinal tract [1, 2]. It is released into circula- tion during apoptotic cell death, and it is believed that it is a surrogate of drug-induced cancer cell death [3]. M30 and M65 are caspase cleaved and intact forms of CK-18, respectively, and they were detected in the circulation by using enzyme-linked immunosorbent assays (ELISAs) [4]. M30 antibody recognizes a neo-epitope of CK-18 formed, therefore it is a more selective biomarker of apoptosis [5, 6]. However, monoclonal antibody M65 measures all CK- 18 fragments that contain full-length epitopes of the pro- tein, which are released during both necrotic and apoptotic A. Bilici Á B. B. O. Ustaalioglu Á M. Seker Á T. Salepci Á M. Gumus Department of Medical Oncology, Dr. Lutfi Kirdar Kartal Education and Research Hospital, Istanbul, Turkey S. Ercan Á A. Orcun Department of Biochemistry, Dr. Lutfi Kirdar Kartal Education and Research Hospital, Istanbul, Turkey A. Bilici (&) Menderes Mah, 364. Sok, Caglar Apt, No: 16, Daire: 1, Esenler, 34210 Istanbul, Turkey e-mail: ahmetknower@yahoo.com 123 Cancer Chemother Pharmacol (2011) 68:309–316 DOI 10.1007/s00280-010-1480-0