Numeric aberration of chromosome 17 is strongly correlated with p53 overexpression, tumor proliferation and histopathology in human bladder cancer

Int J Urol. 1998 Jul;5(4):317-23. doi: 10.1111/j.1442-2042.1998.tb00358.x.

Abstract

Background: This study investigated the relationships between the numeric aberrations of chromosome 17 and p53 expression, the proliferating cell nuclear antigen labeling index (PCNA-LI) and histopathology, to determine their prognostic significance in bladder cancer.

Methods: Using in situ hybridization (ISH) with a biotin-labeled chromosome-specific DNA probe, the copy number of pericentromeric sequences in chromosome 17 were detected within interphase nuclei in formalin-fixed paraffin-embedded sections from 59 nonmetastasized transitional cell carcinomas (TCCs) of the urinary bladder. Expression of p53 and PCNA-LI were determined in serial sections by an immunohistochemical method.

Results: The percentage of hyperdiploid cells for chromosome 17 correlated with p53 overexpression (P< 0.002), PCNA-LI (P< 0.002), increasing tumor grade (P< 0.002) and advanced pathologic stage (P< 0.002). The average percentage of hyperdiploid cells was lower in tumors with negative p53 expression than in tumors with p53 overexpression (P< 0.002). Also, more polysomic TCCs were found in muscle-invasive than in superficial cases (P< 0.01 ), and there was a difference in both p53 overexpression or PCNA-LI between disomic and polysomic TCCs (P< 0.01). Patients with chromosome 17 disomic tumors showed less frequent tumor progression than patients with polysomic tumors (P< 0.05). However, chromosome 17 polysomy was an independent prognostic indicator only for patient survival (P< 0.05).

Conclusion: The occurrence and extent of numeric aberrations of chromosome 17 may be associated with the evolution of aggressive growth in TCC and may be a useful indicator for survival.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Centromere / genetics
  • Chromosome Aberrations*
  • Chromosomes, Human, Pair 17*
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • In Situ Hybridization
  • Interphase / genetics
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Phenotype
  • Prognosis
  • Proliferating Cell Nuclear Antigen / genetics
  • Survival Analysis
  • Tumor Suppressor Protein p53 / genetics*
  • Urinary Bladder Neoplasms / genetics*
  • Urinary Bladder Neoplasms / mortality

Substances

  • Proliferating Cell Nuclear Antigen
  • Tumor Suppressor Protein p53