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The prognostic value of Stathmin-1, S100A2, and SYK proteins in ER-positive primary breast cancer patients treated with adjuvant tamoxifen monotherapy: an immunohistochemical study

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Abstract

Introduction

We recently found that DNA methylation of S100A2, spleen tyrosine kinase (SYK), and Stathmin-1 (STMN1) correlates with response to tamoxifen therapy in metastatic breast cancer. In this retrospective study, we investigated immunohistochemically whether these three markers are predictors of relapse in early breast cancer (EBC) patients treated with adjuvant tamoxifen alone.

Methods

Immunohistochemical staining was performed for S100A2, SYK and STMN1 on a tissue microarray containing ER-positive invasive breast carcinomas from a study cohort of 215 operable breast cancer patients, who underwent radical local therapy and who were treated with adjuvant tamoxifen monotherapy. Cox regression was used to correlate staining intensity of the three markers with main endpoints in our study; disease-free survival (DFS), and disease-specific survival (DSS).

Results

In univariate analysis, only STMN1 staining intensity strongly correlated with DFS (P = 0.014) and DSS (P = 0.002). In the groups of low and high STMN1 intensity, DFS was 84% and 63%, and DSS was 89% and 70%. STMN1 retained its prognostic value for DFS (P = 0.002) and DSS (<0.001) in the multivariate model together with lymph node status. We found also a trend to better DFS in patients with low STMN1 intensity in both lymph node-positive (P = 0.001) and -negative patients (P = 0.065). As the tumour cells did not express S100A2 (except in one case) the potential prognostic value of this marker was not evaluated.

Conclusions

Staining intensity of STMN1, but not SYK, predicted outcome in our collective of ER- positive tamoxifen treated EBC patients.

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Acknowledgments

This research was supported by the European Union Sixth Framework Programme (LSHC-CT-2003–504586). Conflict of interest statement:Ralf Lesche and Sabine Maier are employees and/or stockholders of Epigenomics AG (Berlin, Germany), a company that aims to commercialize DNA methylation markers, including S100A2, STMN1 and SYK. John Martens, Nadia Harbeck, Manfred Schmitt, Sabine Maier, and John Foekens are inventors of a patent on these DNA methylation markers (WO 2004 035803). This patent has been filed by Epigenomics AG.

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Authors and Affiliations

  1. Institute of Oncology, Zaloška 2, Ljubljana, 1000, Slovenia

    Rastko Golouh, Tanja Cufer & Petra Nussdorfer

  2. Artificial Intelligence Laboratory, University of Ljubljana, Ljubljana, Slovenia

    Aleksander Sadikov

  3. Royal Veterinary and Agriculture University, Frederiksberg, Denmark

    Pernille Autzen Usher & Nils Brünner

  4. Department of Obstetrics and Gynaecology, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany

    Manfred Schmitt

  5. Epigenomics AG, Berlin, Germany

    Ralf Lesche & Sabine Maier

  6. Department of Medical Oncology, Erasmus MC, Rotterdam, The Netherlands

    Mieke Timmermans, John A. Foekens & John W. M. Martens

Authors
  1. Rastko Golouh
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  2. Tanja Cufer
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  3. Aleksander Sadikov
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  4. Petra Nussdorfer
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  5. Pernille Autzen Usher
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  6. Nils Brünner
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  7. Manfred Schmitt
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  8. Ralf Lesche
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  9. Sabine Maier
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  10. Mieke Timmermans
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  11. John A. Foekens
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  12. John W. M. Martens
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Corresponding author

Correspondence to Tanja Cufer.

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Golouh, R., Cufer, T., Sadikov, A. et al. The prognostic value of Stathmin-1, S100A2, and SYK proteins in ER-positive primary breast cancer patients treated with adjuvant tamoxifen monotherapy: an immunohistochemical study. Breast Cancer Res Treat 110, 317–326 (2008). https://doi.org/10.1007/s10549-007-9724-3

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  • DOI: https://doi.org/10.1007/s10549-007-9724-3

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