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

Int J Cancer. 2000 Nov 20;89(6):514-8.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Carcinoma, Transitional Cell / genetics*
  • Carcinoma, Transitional Cell / pathology
  • Chromosome Deletion
  • Chromosomes, Human, Pair 9 / genetics
  • Clone Cells
  • Disease Progression
  • Humans
  • Hyperplasia / genetics
  • Loss of Heterozygosity
  • Microsatellite Repeats
  • Neoplasm Recurrence, Local / genetics
  • Neoplasm Recurrence, Local / pathology
  • Neoplasms, Squamous Cell / genetics
  • Neoplasms, Squamous Cell / pathology
  • Papilloma / genetics
  • Papilloma / pathology
  • Precancerous Conditions / genetics*
  • Precancerous Conditions / pathology
  • Repetitive Sequences, Nucleic Acid
  • Urinary Bladder / pathology*
  • Urinary Bladder / ultrastructure
  • Urinary Bladder Neoplasms / genetics*
  • Urinary Bladder Neoplasms / pathology