Prognostic value of TOP2A gene amplification and chromosome 17 polysomy in early breast cancer

Pathol Oncol Res. 2012 Oct;18(4):885-94. doi: 10.1007/s12253-012-9518-8. Epub 2012 Mar 18.

Abstract

The aim of this study was to analyze the occurrence of TOP2A gene amplification and chromosome 17 polysomy in patients with early breast cancer and to correlate the status of these alterations with the prognostic significance expressed as patients' clinical features and survival. Such concurrent analyses of TOP2A gene status and chromosome 17 polysomy have not been performed before. Study group included 149 consecutive stage I-III patients administered standard multimodality treatment. TOP2A abnormalities were examined by standard fluorescence in situ hybridization (FISH) and developed by our group quantitative real-time PCR (qPCR). TOP2A amplification and deletion assessed by FISH were found in 23% and 7% of the tumours, respectively, and by qPCR in 31% and 11% of the tumours, respectively. Chromosome 17 polysomy was detected in 40% of the cases. TOP2A amplification (by qPCR) correlated with shorter disease-free survival (p = 0.03) and overall survival (p = 0.047), and the prognostic value of TOP2A was confirmed in the multivariate analysis (HR = 3.22, 95% CI 1.09-9.56, p = 0.03). TOP2A gene amplification, but not chromosome 17 polysomy, carries negative prognostic information in early breast cancer. Given the aforementioned results, qPCR might serve as a prognostic tool in determining the patient's prognosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Analysis of Variance
  • Aneuploidy
  • Antigens, Neoplasm / genetics*
  • Breast Neoplasms / diagnosis
  • Breast Neoplasms / genetics*
  • Chromosome Aberrations*
  • Chromosomes, Human, Pair 17*
  • DNA Topoisomerases, Type II / genetics*
  • DNA-Binding Proteins / genetics*
  • Female
  • Gene Amplification*
  • Humans
  • In Situ Hybridization, Fluorescence
  • Kaplan-Meier Estimate
  • Middle Aged
  • Poly-ADP-Ribose Binding Proteins
  • Prognosis
  • Real-Time Polymerase Chain Reaction

Substances

  • Antigens, Neoplasm
  • DNA-Binding Proteins
  • Poly-ADP-Ribose Binding Proteins
  • DNA Topoisomerases, Type II
  • TOP2A protein, human