Genetic analysis of Tp53 from urine sediment as a tool for diagnosing recurrence and residual of bladder carcinoma.
OBJECTIVE
Longitudinal study of Tp53 mutation in urine sediments of 26 patients with mutated primary transitional cell carcinoma (TCC) of the urinary bladder at different time periods after transurethral resection of the bladder (TURB), i.e. before and after the first TURB, prior to the control resection and before treatment of a recurrence.


METHODS
DNA of the critical Tp53 exons 5-8 was anaylzed by temperature gradients (TGGE) and sequence.


RESULTS
(1) In 11 of 12 patients (91.7%) mutation reoccurred with the detection of recurrence of the disease. The mutation frequency in patients without any recurrence was 1 in 8 (12.5%) after a follow-up period of 4-16 months. (2) In 7 of 10 patients, the mutation was no longer detectable in the urine sediment after TURB. (3) The mutation frequency at the control resection 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 samples identical mutations were found by sequence in the recurrent tumor. These results show a significant correlation between the detection of a Tp53 mutation in the urine sediments and tumor recurrence or residual.


CONCLUSIONS
(1) Tp53 mutations in the urine sediment could be a useful indicator of tumor recurrence or tumor residual in patients ( approximately 40%) with primary mutated bladder cancer tissue. (2) These results support the monoclonal seeding theory. (3) The finding of identical mutations at different times indicate that the tumor was never totally removed.
Sachs
M D
MD
Department of Urology, Charité-Hospital of the Humboldt University, Berlin, Germany.
Schlechte
H
H
Lenk
V S
VS
Brenner
S
S
Schnorr
D
D
Fleige
B
B
Ditscherlein
G
G
Loening
S A
SA
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002295:Carcinoma, Transitional Cell / Q000235:genetics* / Q000652:urine*; D004252:DNA Mutational Analysis; D005260:Female; D016158:Genes, p53 / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009364:Neoplasm Recurrence, Local / Q000235:genetics* / Q000652:urine*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000652:urine*; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000652:urine*
D016159:Tumor Suppressor Protein p53