TOP2A gene copy number change in breast cancer

J Clin Pathol. 2014 May;67(5):420-5. doi: 10.1136/jclinpath-2013-202052. Epub 2014 Jan 8.

Abstract

Aims: The clinical significance of TOP2A as a prognostic marker has not been clarified. The aims of this study were to investigate the frequency of TOP2A copy number change; to correlate TOP2A with HER2 status, hormone receptor (HR) status and molecular subtype, and further to explore differences in breast cancer-specific survival according to TOP2A and HER2.

Methods: In this study, TOP2A, HER2 and chromosome 17 copy number were assessed in 670 cases of breast cancer using in situ hybridisation techniques. Gene to chromosome ratios ≥2 were classified as amplification. TOP2A deletion (gene to chromosome ratio ≤0.8) or monosomy (only one signal for both gene and chromosome in more than 75% of nuclei) were classified as gene loss.

Results: A strong association between TOP2A change and HR and HER2 status was found. During the first 5 years after diagnosis, the risk of death from breast cancer was significantly higher for cases with HER2 amplification irrespective of TOP2A status.

Conclusions: TOP2A copy number change was strongly associated with HR and HER2 status and as a prognostic marker TOP2A is probably of limited value.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antigens, Neoplasm / genetics*
  • Biomarkers, Tumor / chemistry
  • Biomarkers, Tumor / genetics*
  • Breast Neoplasms / chemistry
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / mortality
  • Breast Neoplasms / pathology
  • Chromosomes, Human, Pair 17
  • DNA Copy Number Variations*
  • DNA Topoisomerases, Type II / genetics*
  • DNA-Binding Proteins / genetics*
  • Female
  • Gene Amplification
  • Gene Deletion
  • Gene Dosage*
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Immunohistochemistry
  • In Situ Hybridization
  • Kaplan-Meier Estimate
  • Middle Aged
  • Poly-ADP-Ribose Binding Proteins
  • Predictive Value of Tests
  • Prognosis
  • Receptor, ErbB-2 / genetics

Substances

  • Antigens, Neoplasm
  • Biomarkers, Tumor
  • DNA-Binding Proteins
  • Poly-ADP-Ribose Binding Proteins
  • ERBB2 protein, human
  • Receptor, ErbB-2
  • DNA Topoisomerases, Type II
  • TOP2A protein, human