Molecular clonal analysis of recurrent bladder cancer

Abstract

In order to select the optimum therapy for patients at risk of recurrent bladder cancer, it is necessary to know the pathway of recurrence development. However, the origin of recurrent bladder cancer is controversially discussed. Therefore, the aim of our study was to define the clonal origin of recurrent tumors of the bladder using molecular genetic markers. Thirty cases with recurrent bladder cancer (1-4 recurrences per case) were investigated by microsatellite analysis using 4 markers for chromosome 9. PCR was performed according to standard protocols followed by gel electrophoresis and automated analysis using an automated DNA-Sequencer (LI-QOR). In 25 of 30 cases, loss of heterozygosity (LOH) occurred in at least 1 tumor. Identical LOH was detected in 20 cases. In all these cases the same allele was affected. Different LOH patterns were found in 4 cases showing LOH in only 1 tumor and in 1 case with alterations of different markers. In 5 cases, no alterations were detected using these markers. Our results show that the majority of bladder cancer recurrences are characterized by monoclonal origin. These data indicate that recurrence is caused by cell dissemination from the original tumor. For that reason, an early instillation therapy should be performed after transurethral resection.