Papillary urothelial hyperplasia is a clonal precursor to papillary transitional cell bladder cancer

Papilloma and papillary hyperplasia (PH) have been proposed to be the putat ive precursor lesions of papillary transitional-cell carcinoma of the urina ry bladder. We examined 15 PH lesions and 4 papillomas for loss of heterozy gosity (LOH) at 17 microsatellite markers on 9 chromosomal arms. Eight of 1 5 (53%) PHs were clonal, demonstrating LOH of at least 1 microsatellite mar ker. In contrast, none of the papillomas showed any genetic changes among t he markers tested. In PH, chromosomal arm 9q was the most frequently lost ( 4/15), followed by 9p and 18q (n = 2) and, less frequently, 8p, 10q, 11p an d 17p(n = 1). Furthermore, 2 hyperplastic lesions demonstrated LOH at 9q on ly, confirming the notion that allelic tass on chromosomal arm 9q is among the earliest events in bladder-cancer progression. In I patient, identical LOH patterns were observed between PH and a recurrent transitional-cell car cinoma. Our molecular data demonstrate that at least a proportion of PHs re present pre cancerous lesions of the bladder that subsequently progress to papillary bladder cancer. Moreover, chromosomal arm 9q may harbor a tumor-s uppressor gene(s) inactivated in the earliest stages of human bladder tumor igenesis. Int. J. Cancer (Pred. Oncol,) 89:5 14-518, 2000. (C) Wiley-Liss, Inc.