Prognostic significance of thymidine kinase activity in bladder carcinoma.

Abstract

Thymidine kinase (TK) plays a key role in the complimentary or alternative salvage pathway of pyrimidine synthesis. Little is known about the significance of TK activity in bladder carcinoma. The authors examined the activity of TK in 55 patients with bladder carcinoma to determine the prognostic significance of TK activity. TK activity in nonfixed, fresh-frozen specimens of bladder carcinoma and normal bladder tissue was determined by using the diethylaminoethanol cellulose disc method. The activity of TK was approximately two-fold higher in bladder carcinoma specimens compared with normal bladder tissues. The TK activity in muscle-invasive bladder carcinoma was two-fold higher compared with the activity in superficial bladder carcinoma (Ta and T1). In addition, the activity of TK in T1 tumors was two-fold higher compared with the TK activity in Ta tumors. The level of TK activity in Grade 3 bladder tumors was two-fold higher compared with the activity in Grade 1 and Grade 2 tumors. Patients with Ta and T1 bladder carcinoma who had low TK activity had a longer postoperative tumor free period compared with the patients who had high TK activity during the 2 years of follow-up. TK activity was correlated with the activity of thymidine synthase, which is a key enzyme for pyrimidine synthesis in the de novo pathway. This study is the first to demonstrate that the level of TK activity is correlated with both disease stage and tumor grade in patients with bladder carcinoma and that elevated TK activity predicts early recurrence in patients with Ta and T1 disease. These results suggest that the level of TK activity may be used as a prognostic parameter and that TK may be a molecular therapeutic target in patients with bladder carcinoma.