Telomere shortening and chromosomal abnormalities in intestinal metaplasia of the urinary bladder

Michael J. Morton, Shaobo Zhang, Antonio Lopez-Beltran, Gregory T. MacLennan, John Eble, Rodolfo Montironi, Ming Tse Sung, Puay Hoon Tan, Suqin Zheng, Honghong Zhou, Liang Cheng

Research output: Contribution to journalArticle

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Abstract

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: 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 controlnuclei to produce amean 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.

Original languageEnglish
Pages (from-to)6232-6236
Number of pages5
JournalClinical Cancer Research
Volume13
Issue number20
DOIs
StatePublished - Oct 15 2007

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Telomere Shortening
Metaplasia
Chromosome Aberrations
Telomere
Urinary Bladder
Fluorescence In Situ Hybridization
Cystitis
Interphase
Adenocarcinoma
Nucleic Acid Probes
Peptide Nucleic Acids
Chromosomes, Human, Pair 17
Chromosomes, Human, Pair 3
Chromosomes, Human, Pair 7
Paraffin
Carcinogenesis
Research Design

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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Telomere shortening and chromosomal abnormalities in intestinal metaplasia of the urinary bladder. / Morton, Michael J.; Zhang, Shaobo; Lopez-Beltran, Antonio; MacLennan, Gregory T.; Eble, John; Montironi, Rodolfo; Sung, Ming Tse; Tan, Puay Hoon; Zheng, Suqin; Zhou, Honghong; Cheng, Liang.

In: Clinical Cancer Research, Vol. 13, No. 20, 15.10.2007, p. 6232-6236.

Research output: Contribution to journalArticle

Morton, MJ, Zhang, S, Lopez-Beltran, A, MacLennan, GT, Eble, J, Montironi, R, Sung, MT, Tan, PH, Zheng, S, Zhou, H & Cheng, L 2007, 'Telomere shortening and chromosomal abnormalities in intestinal metaplasia of the urinary bladder', Clinical Cancer Research, vol. 13, no. 20, pp. 6232-6236. https://doi.org/10.1158/1078-0432.CCR-07-0121
Morton, Michael J. ; Zhang, Shaobo ; Lopez-Beltran, Antonio ; MacLennan, Gregory T. ; Eble, John ; Montironi, Rodolfo ; Sung, Ming Tse ; Tan, Puay Hoon ; Zheng, Suqin ; Zhou, Honghong ; Cheng, Liang. / Telomere shortening and chromosomal abnormalities in intestinal metaplasia of the urinary bladder. In: Clinical Cancer Research. 2007 ; Vol. 13, No. 20. pp. 6232-6236.
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T1 - Telomere shortening and chromosomal abnormalities in intestinal metaplasia of the urinary bladder

AU - Morton, Michael J.

AU - Zhang, Shaobo

AU - Lopez-Beltran, Antonio

AU - MacLennan, Gregory T.

AU - Eble, John

AU - Montironi, Rodolfo

AU - Sung, Ming Tse

AU - Tan, Puay Hoon

AU - Zheng, Suqin

AU - Zhou, Honghong

AU - Cheng, Liang

PY - 2007/10/15

Y1 - 2007/10/15

N2 - 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: 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 controlnuclei to produce amean 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.

AB - 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: 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 controlnuclei to produce amean 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.

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