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Ep-CAM RNA expression predicts metastasis-free survival in three cohorts of untreated node-negative breast cancer

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Abstract

Epithelial cell adhesion molecule (Ep-CAM) recently received increased attention as a prognostic factor in breast cancer. We aimed to validate the influence of Ep-CAM RNA expression in untreated node-negative breast cancer. Ep-CAM RNA expression was evaluated utilizing microarray-based gene-expression profiling in 194 consecutive node-negative breast cancer patients with long-term follow-up not treated in the adjuvant setting. The prognostic significance of Ep-CAM RNA expression for disease-free survival (DFS), metastasis-free survival (MFS), and breast cancer-specific overall survival (OS) was evaluated in univariate and multivariate analysis adjusted for age, grading, pTstage, ER as well as PR receptor and HER-2 status. Additionally, Ep-CAM RNA expression was compared with immunohistochemistry (IHC) for Ep-CAM in 194 patients. The prognostic impact of Ep-CAM gene expression was validated in further 588 node-negative breast cancer patients. Levels of Ep-CAM RNA expression showed a significant correlation with IHC (P = 0.001) and predicted in univariate analysis DFS (P = 0.001, HR = 2.4), MFS (P = 0.003, HR = 2.5), and OS (P = 0.002, HR = 3.1) accurately. The prognostic influence of Ep-CAM RNA was significant also in multivariate analysis for DFS (P = 0.017, HR = 2.0), MFS (P = 0.049, HR = 1.9), and OS (P = 0.042, HR = 2.3), respectively. The association with MFS was confirmed in an independent validation cohort in univariate (P = 0.006, HR = 1.9) and multivariate (P = 0.035, HR = 1.7) analysis. Ep-CAM RNA correlated with the proliferation metagene (P < 0.001, R=0.425) Nevertheless, in multivariate analysis, Ep-CAM was associated with MFS independent from the proliferation metagene (P = 0.030, HR = 1.8). In conclusion, Ep-CAM RNA expression is associated with poor MFS in three cohorts of untreated node-negative breast cancer.

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Acknowledgment

This study was supported by the BMBF (NGFN project Oncoprofile). We thank Ms. Susanne Lindemann for competent bibliographic assistance.

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Authors and Affiliations

  1. Department of Obstetrics and Gynecology, University Medical Center of the Johannes Gutenberg-University, Langenbeckstr. 1, 55131, Mainz, Germany

    Marcus Schmidt, Ilka Brigitte Petry, Daniel Böhm, Antje Lebrecht, Susanne Gebhard, Marco Battista & Heinz Koelbl

  2. Siemens Medical Solutions, Diagnostics GmbH, Cologne, Germany

    Christian von Törne & Mathias Gehrmann

  3. Department of Medical Biometrics, Epidemiology and Informatics, Johannes Gutenberg University, Mainz, Germany

    Aslihan Gerhold-Ay

  4. Department of Pathology, Johannes Gutenberg University, Mainz, Germany

    Cristina Cotarelo

  5. IfADo-Leibniz Research Centre for Working Environment and Human Factors (IfADo), TU Dortmund University, Dortmund, Germany

    Wiebke Schormann, Evgenia Freis & Jan G. Hengstler

  6. Collaborative Research Center 475, Faculty of Statistics, TU Dortmund University, Dortmund, Germany

    Silvia Selinski, Katja Ickstadt & Jörg Rahnenführer

  7. Department of Medicine III, Johannes Gutenberg University, Mainz, Germany

    Martin Sebastian

  8. Department of Medicine (Cancer Research), West German Cancer Center, University Hospital, Essen, Germany

    Martin Schuler

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  1. Marcus Schmidt
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  2. Ilka Brigitte Petry
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Correspondence to Marcus Schmidt.

Additional information

An invited commentary to this article can be found at doi:10.1007/s10549-010-0932-x

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Schmidt, M., Petry, I.B., Böhm, D. et al. Ep-CAM RNA expression predicts metastasis-free survival in three cohorts of untreated node-negative breast cancer. Breast Cancer Res Treat 125, 637–646 (2011). https://doi.org/10.1007/s10549-010-0856-5

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