Telomere Shortening and Chromosomal Abnormalities in Intestinal Metaplasia of the Urinary Bladder
Clinical Cancer Research
Purpose: 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. Experimental Design:
... xperimental Design: 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). Downloaded from * Telomere intensity was statistically shorter compared with that of the normal cells with P < 0.0001 using Wilcoxon paired signed rank test. c Telomere intensity was statistically shorter compared with that of the normal cells with P = 0.0005 using Wilcoxon signed rank test. b Telomere intensity was statistically shorter compared with that of the normal cells with P = 0.0015 using Wilcoxon signed rank test. x The telomere intensity was significantly shorter compared with cystitis glandularis (P = 0.0015, Wilcoxon signed rank test).