title: Telomere shortening and chromosomal abnormalities in intestinal metaplasia of the urinary bladder.
abstract: OBJECTIVE
  Although intestinal metaplasia is often found in association with adenocarcinoma of the urinary bladder, it is unclear whether intestinal metaplasia of the bladder is a premalignant lesion. Telomere shortening has recently been implicated in epithelial carcinogenesis. We used quantitative fluorescent in situ hybridization (FISH) to measure telomere length and UroVysion FISH to detect cytogenetic abnormalities in urinary bladder specimens with intestinal metaplasia.
  
  
  METHODS
  Paraffin-embedded tissue blocks from 34 patients with intestinal metaplasia of the urinary bladder were evaluated. Twelve of the 34 patients had coexistent cystitis glandularis, and telomere length was measured in these lesions for comparison. Tissue sections were prepared and hybridized with a telomere-specific peptide nucleic acid probe. Quantitative FISH on interphase nuclei was used to assess telomere signal intensity. Additional sections were hybridized with centromeric probes for chromosomes 3, 7, and 17 and a locus-specific probe 9p21. Multicolor FISH was used to analyze for cytogenic abnormalities in the interphase nuclei of intestinal metaplasia.
  
  
  RESULTS
  In all 34 cases, reduced average telomere signal intensity was observed in the nuclei of intestinal metaplasia cells compared with adjacent control nuclei to produce a mean relative intensity of 48.5% (P < 0.0001). When cystitis glandularis was present, significant differences in the telomere-specific signal intensity existed between cystitis glandularis and normal cells (P = 0.0005) and between cystitis glandularis and intestinal metaplasia cells (P = 0.0015). Three of the 34 cases showed chromosomal gains in the UroVysion FISH assay.
  
  
  CONCLUSIONS
  Our findings indicate that intestinal metaplasia in the urinary bladder is associated with significant telomere shortening relative to telomere length in adjacent normal urothelial cells. These lesions also occasionally showed cytogenetic abnormalities associated with telomere shortening. Our findings support the hypothesis that intestinal metaplasia of the urinary bladder is a precursor lesion to and could be a marker in the development of adenocarcinoma of the urinary bladder.
authors.affiliation: Department of Pathology, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Morton
authors.forename: Shaobo
authors.initials: S
authors.lastname: Zhang
authors.forename: Antonio
authors.initials: A
authors.lastname: Lopez-Beltran
authors.forename: Gregory T
authors.initials: GT
authors.lastname: MacLennan
authors.forename: John N
authors.initials: JN
authors.lastname: Eble
authors.forename: Rodolfo
authors.initials: R
authors.lastname: Montironi
authors.forename: Ming-Tse
authors.initials: MT
authors.lastname: Sung
authors.forename: Puay-Hoon
authors.initials: PH
authors.lastname: Tan
authors.forename: Suqin
authors.initials: S
authors.lastname: Zheng
authors.forename: Honghong
authors.initials: H
authors.lastname: Zhou
authors.forename: Liang
authors.initials: L
authors.lastname: Cheng
mesh_terms: D000230:Adenocarcinoma / Q000209:etiology / Q000235:genetics; D002869:Chromosome Aberrations; D002875:Chromosomes / Q000648:ultrastructure; D003556:Cystitis / Q000150:complications; D003582:Cytogenetics; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D017404:In Situ Hybridization, Fluorescence; D007422:Intestines / Q000473:pathology*; D008679:Metaplasia / Q000235:genetics / Q000473:pathology*; D011230:Precancerous Conditions / Q000235:genetics; D016615:Telomere / Q000648:ultrastructure*; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000473:pathology*