Pronounced Microsatellite Instability in Transitional Cell Carcinomas from Young Patients with Bladder Cancer

Microsatellites may show loss of heterozygosity as well as instability of the repeats. We examined 22 different microsatellites in 14 bladder tumours (7 grade II non-invasive, 7 grade III/IV invasive) and found altered CA repeat length compared with leukocytes, indicating instability, in several microsatellites in all tumours. Instability was significantly more frequent in low stage tumours compared with high stage tumours. The number of new bands occuring was also significantly higher in low stage tumours (median 7.2) compared with high stage tumours (median 3.3). Furthermore, patients with a disease course > or = 1 year had significantly more unstable microsatellites (10.83) than those with a disease course < 1 year (mean 8.88). Examination of biopsies from normal bladder mucosa showed no instability. In 2 cases in which selected site biopsies were taken, alterations differed from the tumours, pointing at a different clonal development. LOH was most frequent in 9p markers in low stage tumours. In a group of markers located at 2p, 17p (p53), 9q, 5q and 10p, LOH was significantly more frequent in high stage tumours. Microsatellites placed at MSH2 and MLH1 loci showed LOH in several cases, indicating that the profound microsatellite instability could partly be an effect of damage to these genes.