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Breast Cancer Research and Treatment

, Volume 113, Issue 3, pp 457–466 | Cite as

Gene expression of topoisomerase II alpha (TOP2A) by microarray analysis is highly prognostic in estrogen receptor (ER) positive breast cancer

  • A. Rody
  • T. Karn
  • E. Ruckhäberle
  • V. Müller
  • M. Gehrmann
  • C. Solbach
  • A. Ahr
  • R. Gätje
  • U. Holtrich
  • M. Kaufmann
Preclinical Study

Abstract

Introduction Overexpression of Topoisomerase II alpha (TOP2A) has been implicated with gene amplification of the 17q21 amplicon and consecutively with ErbB2 overexpression and amplification. However, gene amplification does not necessarily correlate with RNA and protein expression. There is growing evidence that TOP2A protein expression is a strong prognostic and TOP2A gene amplification might be a predictive marker (particularly for the use of anthracyclines). Methods Large scale analysis was performed using Affymetrix microarray data from n = 1,681 breast cancer patients to evaluate TOP2A expression. Results TOP2A expression showed a strong correlation with tumor size (χ2-test, P < 0.001), grading (P < 0.001), ErbB2 (P < 0.001) and Ki67 expression (P < 0.001) as well as nodal status (P = 0.042). Survival analysis revealed a significant prognostic value in ER positive (n = 994; log rank P < 0.001), but not in ER negative breast cancer patients (n = 369, P = 0.35). The prognostic impact of TOP2A expression was independent of Ki67 expression in ER positive tumors (P = 0.002 and P = 0.007 for high and low Ki67, respectively). Moreover a worse prognosis of high TOP2A expressing tumors was found in the subgroup of ErbB2 negative tumors (P < 0.001) and a trend among ErbB2 positive tumors (P = 0.11). The prognostic value of TOP2A was independent of whether the patients were untreated or had received adjuvant therapy. In multivariate Cox regression analysis including standard parameters TOP2A emerged to be the top prognostic marker (HR 2.40, 95% CI 1.68–3.43, P < 0.001). Conclusion TOP2A expression is an independent prognostic factor in ER positive breast cancer and could be helpful for risk assessment in ER positive breast cancer patients.

Keywords

Breast breast cancer Microarray analysis Prognosis Topoisomerase II alpha 

Notes

Acknowledgements

We thank Katherina Kourtis and Samira Adel for expert technical assistance. This work was supported by grants from the Deutsche Krebshilfe, the Margarete Bonifer-Stiftung, Bad Soden, the BANSS-Stiftung, Biedenkopf, and the Dr. Robert Pfleger-Stiftung, Bamberg.

Supplementary material

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(DOC 100 kb)
10549_2008_9964_MOESM2_ESM.pdf (104 kb)
(DOC 105 kb)

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Copyright information

© Springer Science+Business Media, LLC. 2008

Authors and Affiliations

  • A. Rody
    • 1
  • T. Karn
    • 1
  • E. Ruckhäberle
    • 1
  • V. Müller
    • 2
  • M. Gehrmann
    • 3
  • C. Solbach
    • 1
  • A. Ahr
    • 1
  • R. Gätje
    • 1
  • U. Holtrich
    • 1
  • M. Kaufmann
    • 1
  1. 1.Department of Obstetrics and GynecologyJ. W. Goethe UniversityFrankfurtGermany
  2. 2.Department of Obstetrics and GynecologyUniversity of HamburgHamburgGermany
  3. 3.Siemens DiagnosticsLeverkusenGermany

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