Published in Cancer Detection and Prevention 2000; 24(1):24-32.

Progression in Transitional Cell Carcinomaof the Urinary Bladder Analysis of Tp53 Gene Mutations by Temperature Gradients and Sequence inTumor Tissuesand in Cellular Urine Sediments

Horst H Schlechte PhD, Markus D Sachs, Severin V Lenk, Sebastian Brenner MD, Birgit D Rudolph Ph.D., and Stephan A Loening Prof.

Department of Urology, Charité Hospital of the Humboldt-University, Berlin, Germany Department of Pediatrics, University Clinic Carl Gustav Carus, Technical University, Dresden, Germany Institute of Pathology, Charité Hospital of the Humboldt-University, Berlin, Germany

Address all correspondence ta: Dr. H.H. Schlechte Department of Urology. Charité, Humboldt-University Schumannstr. 20/21, 010117 Berlin, Germany Telephone: +49-30-28023702 Fax: +49-30-28025469

ABSTRACT The relationship between expression of p53 protein in bladder cancer and tumor progression isknown. 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. Thesepatients were followed up for at least three months. Separate polymerase chain reactions (PCR) were carried out forexons 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 reamplitied mutant and wild-type hands 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 ofpatients with Tp53 mutated cancer, seven of 12 had a tumor progression. In II of 14 patients with ‘[p53 mutation incancer tissue, the same mutation was also found in urine sediments. In such patients, successful tumor treatment byTURB results in loss of their Tp53 mutation in urine sediment, and tumor recurrency resulted in reappearance.

KEY WORDS: bladder, cancer, progression, p53, mutation, urine.

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