PRONOUNCED MICROSATELLITE INSTABILITY IN TRANSITIONAL-CELL CARCINOMASFROM 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 bladde r tumours (7 grade II non-invasive, 7 grade III/IV invasive) and found altered CA repeat length compared with leukocytes, indicating instabi lity, in several microsatellites in all tumours. Instability was signi ficantly more frequent in low stage tumours compared with high stage t umours. The number of new bands occuring was also significantly higher in low stage tumours (median 7.2) compared with high stage tumours (m edian 3.3). Furthermore, patients with a disease course greater than o r equal to 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 ca ses in which selected site biopsies were taken, alterations differed f rom the tumours, pointing at a different clonal development. LOH was m ost 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 MLH 1 loci showed LOH in several cases, indicating that the profound micro satellite instability could partly be an effect of damage to these gen es. Int. J. Cancer (Pred. Oncol.) 79:396-401, 1998. (C) 1998 Wiley-Lis s, Inc.