title: Papillary urothelial hyperplasia is a clonal precursor to papillary transitional cell bladder cancer.
abstract: Papilloma and papillary hyperplasia (PH) have been proposed to be the putative precursor lesions of papillary transitional-cell carcinoma of the urinary bladder. We examined 15 PH lesions and 4 papillomas for loss of heterozygosity (LOH) at 17 microsatellite markers on 9 chromosomal arms. Eight of 15 (53%) PHs were clonal, demonstrating LOH of at least 1 microsatellite marker. In contrast, none of the papillomas showed any genetic changes among the 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 and 17p (n = 1). Furthermore, 2 hyperplastic lesions demonstrated LOH at 9q only, confirming the notion that allelic loss on chromosomal arm 9q is among the earliest events in bladder-cancer progression. In 1 patient, identical LOH patterns were observed between PH and a recurrent transitional-cell carcinoma. Our molecular data demonstrate that at least a proportion of PHs represent pre-cancerous lesions of the bladder that subsequently progress to papillary bladder cancer. Moreover, chromosomal arm 9q may harbor a tumor-suppressor gene(s) inactivated in the earliest stages of human bladder tumorigenesis.
authors: The James Buchanan Brady Urological Institute, Johns Hopkins Hospital, Baltimore, MD, USA.
authors: N H
authors: NH
authors: Chow
authors: P
authors: P
authors: Cairns
authors: C F
authors: CF
authors: Eisenberger
authors: M P
authors: MP
authors: Schoenberg
authors: D C
authors: DC
authors: Taylor
authors: J I
authors: JI
authors: Epstein
authors: D
authors: D
authors: Sidransky
mesh_terms: D002295:Carcinoma, Transitional Cell / Q000235:genetics* / Q000473:pathology; D002872:Chromosome Deletion; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics; D002999:Clone Cells; D018450:Disease Progression; D006801:Humans; D006965:Hyperplasia / Q000235:genetics; D019656:Loss of Heterozygosity; D018895:Microsatellite Repeats; D009364:Neoplasm Recurrence, Local / Q000235:genetics / Q000473:pathology; D018307:Neoplasms, Squamous Cell / Q000235:genetics / Q000473:pathology; D010212:Papilloma / Q000235:genetics / Q000473:pathology; D011230:Precancerous Conditions / Q000235:genetics* / Q000473:pathology; D012091:Repetitive Sequences, Nucleic Acid; D001743:Urinary Bladder / Q000473:pathology* / Q000648:ultrastructure; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000473:pathology