title: Short telomeres and chromosome instability prior to histologic malignant progression and cytogenetic aneuploidy in papillary urothelial neoplasms.
abstract: OBJECTIVE
  Evaluation of the relationships existing among 3 histologic types of urothelial tumors, chromosomal instability, and telomere length.
  
  
  METHODS
  We examined 37 consecutive cases of papillary urothelial neoplasm, from which 26 (70.3%) were suitable for karyotype analysis, comprising 7 papillary urothelial neoplasms of low malignant potential (PUNLMPs), 10 low-grade papillary urothelial carcinomas (PUCs), and 9 high-grade PUCs. We performed karyotype and anaphase bridge analyses, and measured telomere lengths by quantitative fluorescence in situ hybridization.
  
  
  RESULTS
  PUNLMPs were always diploid and had anaphase bridges. Low-grade PUCs showed diploidy (n = 2), hypoploidy (n = 4) and polyploidy (n = 4), and high-grade PUCs showed diploidy (n = 1) and polyploidy (n = 8); both had anaphase bridges. The incidence of anaphase bridges did not differ significantly between PUNLMPs and high-grade PUCs (P = 0.105). The telomere lengths of PUNLMP, low-grade PUC, and high-grade PUC, expressed as mean telomere fluorescence units (TFU) ± SD, were 7906 ± 3197, 4893 ± 1567, and 3299 ± 1406, respectively. The differences among the 3 groups were significant. However, 42.9% of the PUNLMPs had shorter telomeres than the mean value for low-grade PUCs, and 30.0% of the low-grade PUCs had shorter telomeres than those for high-grade PUCs. There was an inverse correlation between telomere length and the incidence of anaphase bridges.
  
  
  CONCLUSIONS
  PUNLMP appears to progress to low-grade PUC and high-grade PUC in association with telomere shortening and chromosomal instability. Our data suggest that critically shortened telomeres cause chromosomal instability during progression of papillary urothelial neoplasms.
authors.affiliation: Research Team for Geriatric Pathology, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan.
authors.forename: Naotaka
authors.initials: N
authors.lastname: Izumiyama-Shimomura
authors.affiliation: Research Team for Geriatric Pathology, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan.
authors.forename: Ken-Ichi
authors.initials: K
authors.lastname: Nakamura
authors.affiliation: Research Team for Geriatric Pathology, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan; Department of Pathology, Tokyo Metropolitan Geriatric Hospital, Tokyo, Japan.
authors.forename: Junko
authors.initials: J
authors.lastname: Aida
authors.affiliation: Research Team for Geriatric Pathology, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan.
authors.forename: Naoshi
authors.initials: N
authors.lastname: Ishikawa
authors.affiliation: Department of Pathophysiology, Yokohama College of Pharmacy, Yokohama, Japan.
authors.forename: Mie
authors.initials: M
authors.lastname: Kuroiwa
authors.affiliation: Department of Laboratory Medicine, Hadano Red Cross Hospital, Hadano, Kanagawa-ken, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Hiraishi
authors.affiliation: Department of Pathology and Laboratory Medicine, Japanese Red Cross Medical Center, Tokyo, Japan.
authors.forename: Mutsunori
authors.initials: M
authors.lastname: Fujiwara
authors.affiliation: Division of Pathology, The Cancer Institute, Japanese Foundation for Cancer Research, Tokyo, Japan.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Ishikawa
authors.affiliation: Division of Pathology, The Cancer Institute, Japanese Foundation for Cancer Research, Tokyo, Japan.
authors.forename: Naoko
authors.initials: N
authors.lastname: Inoshita
authors.affiliation: Department of Urology, The Cancer Institute Hospital, Tokyo, Japan.
authors.forename: Junji
authors.initials: J
authors.lastname: Yonese
authors.affiliation: Bioinformatics Group, Genome Center and Department of Cancer Genomics, The Cancer Institute, The Japanese Foundation for Cancer Research, Tokyo, Japan.
authors.forename: Masaaki
authors.initials: M
authors.lastname: Matsuura
authors.affiliation: Terry Fox Laboratory, British Columbia Cancer Research Centre, Vancouver, BC, Canada.
authors.forename: Steven S S
authors.initials: SS
authors.lastname: Poon
authors.affiliation: Department of Pathology, Tokyo Metropolitan Geriatric Hospital, Tokyo, Japan.
authors.forename: Tomio
authors.initials: T
authors.lastname: Arai
authors.affiliation: Research Team for Geriatric Pathology, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan; Department of Pathology, Tokyo Metropolitan Geriatric Hospital, Tokyo, Japan. Electronic address: takubo@tmig.or.jp.
authors.forename: Kaiyo
authors.initials: K
authors.lastname: Takubo
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000705:Anaphase / Q000235:genetics; D000782:Aneuploidy; D002291:Carcinoma, Papillary / Q000235:genetics* / Q000473:pathology; D002295:Carcinoma, Transitional Cell / Q000235:genetics* / Q000473:pathology; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D043171:Chromosomal Instability; D020732:Cytogenetic Analysis; D018450:Disease Progression; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D059785:Karyotype; D008875:Middle Aged; D032681:Spectral Karyotyping; D016615:Telomere; D059506:Telomere Shortening; D014571:Urologic Neoplasms / Q000235:genetics* / Q000473:pathology
keywords: Anaphase bridge; Chromosomal instability; Karyotype analysis; PUNLMP; Q-FISH; Telomere; Urothelial carcinoma