Progression in transitional cell carcinoma of the urinary bladder--analysis of Tp53 gene mutations by temperature gradients and sequence in tumor tissues and in cellular urine sediments.

Abstract

The relationship between expression of p53 protein in bladder cancer and tumor progression is known. In this paper, we attempt to study this phenomenon by molecular-genetic techniques. One hundred thirty-seven bladder tumor tissues were obtained from transurethral resection (TURB). Urine sediments were collected from 72 patients suffering from transitional cell carcinoma and tumor recurrence. These patients were followed up for at least three months. Separate polymerase chain reactions (PCR) were carried out for exons 5, 6, 7, and 8 of the Tp53 gene. Temperature gradient gel electrophoresis (TGGE) was used to screen mutations in the PCR products. Sequencing from reamplified mutant and wildtype bands was excised from the TGGE. Tp53 mutation frequency is 43.1% in 137 bladder cancer specimens, but already 32.7% of Ta-tumors (16/49) were Tp53 mutated. Four of 25 patients with Tp53 wild-type tumors suffered from progression. In the group of patients with Tp53 mutated cancer, seven of 12 had a tumor progression. In 11 of 14 patients with Tp53 mutation in cancer tissue, the same mutation was also found in urine sediments. In such patients, successful tumor treatment by TURB results in loss of their Tp53 mutation in urine sediment, and tumor recurrency resulted in reappearance.