Comparison of topoisomerase-IIalpha gene status between primary breast cancer and corresponding distant metastatic sites

Breast Cancer Res Treat. 2003 Feb;77(3):199-204. doi: 10.1023/a:1021874224490.


Background: Topoisomerase-IIalpha (topo-IIalpha) is a key enzyme in DNA replication and a molecular target for anticancer drugs called topoisomerase-II inhibitors, such as anthracyclines. Its value as a predictive marker of responsiveness to these cytotoxic drugs is currently being evaluated with promising results. However, even in the metastatic setting, the choice of treatment is based on the biologic characteristics of the primary tumor. Few data are available regarding the expression of biological markers between the primary tumor and the corresponding distant metastases.

Methods: Topo-IIalpha gene status was evaluated in 29 breast cancer patients in which a primary tumor sample and a corresponding metastatic sample were both available. Fluorescent in situ hybridization (FISH) with the Vysis triple probe (Vysis multi-color topo-IIalpha spectrum orange, Her-2 spectrum green and CEP17 spectrum aqua probe) was used, which allowed the concomitant evaluation of HER-2 gene status.

Results: As previously reported, topo-IIalpha gene aberrations are always associated with HER-2 gene amplification; indeed no topo-IIalpha gene aberrations have been observed in the HER-2 negative tumors. Conversely, 38.5% (five patients) of the HER-2 positive primary breast tumors (13 patients) were topo-IIalpha amplified, while 61.5% (eight patients) had a normal topo-IIalpha gene. No topo-IIalpha gene deletion was found in our series. Topo-IIalpha gene amplification in the primary tumor was always associated with amplification in the corresponding metastases, and no metastases with topo-IIalpha gene amplification were seen without amplification in the primary tumor. Furthermore, the amplification level of topo-IIalpha (i.e., ratio topo-IIalpha:CEP17) remained unchanged in primary and metastatic sites.

Conclusion: Despite the low number of patients, our results seem to indicate that topo-IIalpha gene status evaluation in the primary breast tumor accurately reflects its status in the corresponding distant metastases.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Anthracyclines / administration & dosage
  • Antigens, Neoplasm
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Biomarkers, Tumor / genetics
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / genetics
  • Breast Neoplasms / pathology*
  • DNA Topoisomerases, Type II / analysis
  • DNA Topoisomerases, Type II / genetics*
  • DNA-Binding Proteins
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • In Situ Hybridization, Fluorescence
  • Middle Aged
  • Neoplasm Metastasis / genetics
  • Neoplasm Metastasis / pathology*
  • Predictive Value of Tests
  • Receptor, ErbB-2 / genetics*


  • Anthracyclines
  • Antigens, Neoplasm
  • Biomarkers, Tumor
  • DNA-Binding Proteins
  • Receptor, ErbB-2
  • DNA Topoisomerases, Type II