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

The relationship between expression of p53 protein in bladder cancer and tu mor progression is known. In this paper, we attempt to study this phenomeno n by molecular-genetic techniques. One hundred thirty-seven bladder tumor t issues were obtained from transurethral resection (TURB). Urine sediments w ere collected from 72 patients suffering from transitional cell carcinoma a nd tumor recurrence. These patients were followed up for at least three mon ths. Separate polymerase chain reactions (PCR) were carried out for exons 5 , 6, 7, and 8 of the Tp53 gene. Temperature gradient gel electrophoresis (T GGE) was used to screen mutations in the PCR prod ucts. Sequencing from rea mplified 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 T a-tumors (16/49) were Tp53 mutated. Four of 25 patients with Tp53 wild-type rumors suffered from progression. In the group of patients with Tp53 mutat ed cancer, seven of 12 had a tumor progression. In 11 of 14 patients with T p53 mutation in cancer tissue, the same mutation was also found in urine se diments. In such patients, successful tumor treatment by TURB results in lo ss of their Tp53 mutation in urine sediment, and tumor recurrency resulted in reappearance.