Zhang 10_6

Reliable markers for monitoring bladder tumor therapy are needed to evaluate treatment effectiveness. Thymidine kinase 1 (TK1) is an enzyme involved in DNA synthesis and therefore proliferation-dependent. Serum concentration of TK1 (STK1) correlates with malignancy in various types of cancer, thus reflecting treatment results. This study explores for the first time the use of STK1 concentration, both as a prognostic marker and to monitor the outcome of bladder carcinoma surgery. STK1 in 56 bladder carcinoma patients was measured pre-operatively, and postoperatively at 1 week and 1, 3, and 6 months, using an immune ECL dot blot assay. An anti-TK1 chicken IgY antibody was used to determine STK1 concentrations. Mean pre-operative STK1 of bladder carcinoma patients was significantly higher than that of healthy individuals, with no overlap of individual values. STK1 concentrations increased significantly with tumor stage (I-III) and T-values (T1-T2), but not tumor grade (G1-G4). STK1 gradually declined, being 66% lower after 1 week. STK1 reached the level of healthy controls at 1 month and remained there for at least 6 months, post-operatively until this study ended. Since STK1 concentration correlates with tumor stage, degree of invasion and metastasis, and monitors the surgical outcome, it can be a reliable index to diagnose and determine prognosis in post-operative bladder carcinoma. Introduction Tumor markers are still not fully accepted in clinical use, although several have been used for decades. In bladder carcinoma, the use of biomarkers in detecting superficial disease or predicting the clinical outcome of individual tumors is limited and controversial. Carcinoembryonic antigens (CEA), CA125 and CA19.9 can be used to monitor patients with advanced malignancy (1,2), while CEA CA50, and CA19 and tissue polypeptide antigen (TPA) have been used to distinguish surface from invasive tumors (3). TPA is a circulating complex of polypeptide fragments from cytokeratin 8, 18 and 19, which has been used for years. TPA levels are significantly higher in the serum and urine of patients with bladder cancer than in controls. However, no difference was found in the TPA levels between superficial and invasive bladder cancers (4). Cytokeratin 19 (CYFRA 21-1) might play a role in diagnosing bladder cancer and assist urologists in detecting bladder cancer as a non-invasive adjunct to cytoscopy (5). It might also be a useful marker in diagnosing transitional cell carcinoma as it is sensitive to low-grade disease (6). Tissue polypeptide-specific antigen (TPS) and polyclonal antibodies against cytokeratin 18 are also tumor markers for following up and establishing prognosis of bladder cancer. Serum TPS shows a correlation to stage, urine cytology, and tumor shape and size. There is a significant correlation between TPS and stage, presence of metastatic lymph nodes, metastasis, urinary cytology, and tumor shape and tumor size. However, grade, number of tumors, relapses, and recurrences were not significantly correlated with serum TPS, and do not appear to be useful in the follow-up of patients with bladder disease (7). It is clear that serum cytokeratin-18 level increases in patients with bladder cancer. However, cytokeratin-18 is only useful as a tumor marker in diagnosing T3 and higher stage tumors, but has no diagnostic value in lower stage bladder cancers (8). In evaluating the individual and combined use of three cytokeratin fragments, i.e. CYFRA 21-1, TPA, and TPS, in the serum of bladder cancer patients, the sensitivity of each of the three markers was found to increase with advancing tumor stage and grade. Combining 2 of the 3 markers did not ONCOLOGY REPORTS 15: 455-461, 2006 455 Thymidine kinase 1: A proliferation marker for determining prognosis and monitoring the surgical outcome of primary bladder carcinoma patients JIE ZHANG1, QUANAN JIA1, SHAN ZOU1, PINGAN ZHANG2, XIAOBING ZHANG1, SVEN SKOG3, PENGCHENG LUO1, WEI ZHANG1 and QIMIN HE3 Departments of 1Urology and 2Laboratory Science, RenMin Hospital of Wuhan University, Wuhan 430060, P.R. China; 3Department of Oncology Clinical Research Laboratory, Clinical Research Centre, Karolinska University Hospital, Karolinska Institute, S-14186, Stockholm, Sweden Received June 10, 2005; Accepted August 19, 2005 _________________________________________ Correspondence to: Dr Qimin He, Department of Oncology Clinical Research Laboratory, Clinical Research Centre, Karolinska University Hospital (Huddinge), Karolinska Institute, S-14186