Genetic analysis of Tp53 from urine sediment as a tool for diagnosing recurrence and residual of bladder carcinoma

Objectives: Longitudinal study of Tp53 mutation in urine sediments of 26 pa tients with mutated primary transitional cell carcinoma (TCC) of the urinar y bladder at different time periods after transurethral resection of the bl adder (TURB), i.e. before and after the first TUBS, prior to the control re section and before treatment of a recurrence. Methods: DNA of the critical Tp53 exons 5-8 was anaylzed by temperature gra dients (TGGE) and sequence. Results:(1) In 11 of 12 patients (91.7%) mutation reoccurred with the detec tion of recurrence of the disease. The mutation frequency in patients witho ut any recurrence was 1 in 8 (12.5%) after a follow-up period of 4-16 month s. (2) In 7 of 10 patients, the mutation was no longer detectable in the ur ine sediment after TURB. (3) The mutation frequency at the control resectio n 6 weeks after the first TURB was 5 in 7 (71.4%) in patients found to have residual and 1 in 7 (14.2%) in the tumor-free patients. (4) In 9 of 10 sam ples identical mutations were found by sequence in the recurrent tumor. The se results show a significant correlation between the detection of a Tp53 m utation in the urine sediments and tumor recurrence or residual. Conclusions: (1) Tp53 mutations in the urine sediment could be a useful ind icator of tumor recurrence or tumor residual in patients (similar to 40%) w ith primary mutated bladder cancer tissue. (2) These results support the mo noclonal seeding theory. (3) The finding of identical mutations at differen t times indicate that the tumor was never totally removed. Copyright (C) 20 00 S. Karger AG, Basel.