title: Deletions of chromosomes 9 and 8p in histologically normal urothelium of patients with bladder cancer.
abstract: OBJECTIVE
  Multifocality and frequent recurrence of urothelial carcinoma of the urinary bladder indicate a disease of the entire "urothelial field", but little is known about chromosomal alterations in histologically normal urothelium. Histopathologically normal urothelium from patients with and without concurrent urothelial carcinoma was analyzed for loss of heterozygosity (LOH) on chromosomes 8p, 9 and 17p, regions that are known to play an important role in urothelial carcinogenesis.
  
  
  METHODS
  Histologically inconspicuous urothelial mucosa samples (n = 160) from cystectomy specimens of patients with urothelial carcinoma (n = 15, max. diagnosis: CIS, pT1-4; all tumors grade 3) were studied. Control samples (n = 50) were obtained from patients with benign prostatic hyperplasia (n = 30) and from cystectomies performed for invasive non-urothelial carcinoma (n = 20). Tissue samples were laser-microdissected and DNA was isolated using standard protocols. LOH analyses were performed using 16 polymorphic markers on chromosomes 8p, 9p/q and 17p.
  
  
  RESULTS
  All investigated samples were informative for at least one microsatellite marker on each chromosome/chromosomal arm. Deletions were found on chromosome 9 and/or 8p in 15/160 (9.4%) of normal urothelial samples from urothelial cancer patients. These alterations were only found in 5/15 patients with urothelial carcinoma. There were no deletions on chromosome 17p. The marker D9S1113 on chromosome 9q33-34 was most frequently affected (11/15 samples, 73%). No chromosomal deletions were found in any of the 50 urothelial control samples.
  
  
  CONCLUSIONS
  Specific genetic alterations frequently associated with bladder cancer are detectable in histologically normal urothelium of patients with bladder cancer, supporting the field effect hypothesis in urothelial carcinogenesis. However, intramucosal spread of tumor cells that escape light microscopic detection remains a possibility, since normal urothelium and concurrent carcinomas showed matching deletions. Chromosomal deletions in normal bladder mucosa are not a common finding and argue against a frequent genomic alteration of the entire urothelial field in bladder carcinogenesis.
authors.affiliation: Department of Urology, University of Regensburg, Franz-J.-S.-Allee 11, 93042 Regensburg, Germany. robert.stoehr@klinik.uni-regensburg.de
authors.forename: Robert
authors.initials: R
authors.lastname: Stoehr
authors.forename: Sabrina
authors.initials: S
authors.lastname: Zietz
authors.forename: Maximilian
authors.initials: M
authors.lastname: Burger
authors.forename: Thomas
authors.initials: T
authors.lastname: Filbeck
authors.forename: Stefan
authors.initials: S
authors.lastname: Denzinger
authors.forename: Ellen C
authors.initials: EC
authors.lastname: Obermann
authors.forename: Christine
authors.initials: C
authors.lastname: Hammerschmied
authors.forename: Wolf F
authors.initials: WF
authors.lastname: Wieland
authors.forename: Ruth
authors.initials: R
authors.lastname: Knuechel
authors.forename: Arndt
authors.initials: A
authors.lastname: Hartmann
mesh_terms: D000368:Aged; D002872:Chromosome Deletion; D002874:Chromosome Mapping; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics*; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D001749:Urinary Bladder Neoplasms / Q000235:genetics*; D019459:Urothelium