Short telomeres and chromosome instability prior to histologic malignant progression and cytogenetic aneuploidy in papillary urothelial neoplasms

Urol Oncol. 2014 Feb;32(2):135-45. doi: 10.1016/j.urolonc.2012.12.005. Epub 2013 Mar 17.


Purpose: Evaluation of the relationships existing among 3 histologic types of urothelial tumors, chromosomal instability, and telomere length.

Patients and 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.

Keywords: Anaphase bridge; Chromosomal instability; Karyotype analysis; PUNLMP; Q-FISH; Telomere; Urothelial carcinoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Anaphase / genetics
  • Aneuploidy*
  • Carcinoma, Papillary / genetics*
  • Carcinoma, Papillary / pathology
  • Carcinoma, Transitional Cell / genetics*
  • Carcinoma, Transitional Cell / pathology
  • Cell Transformation, Neoplastic / genetics
  • Chromosomal Instability*
  • Cytogenetic Analysis
  • Disease Progression
  • Humans
  • In Situ Hybridization, Fluorescence
  • Karyotype
  • Middle Aged
  • Spectral Karyotyping
  • Telomere
  • Telomere Shortening*
  • Urologic Neoplasms / genetics*
  • Urologic Neoplasms / pathology