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Tissue kallikrein-related peptidase 4 (KLK4), a novel biomarker in triple-negative breast cancer

  • Feng Yang , Michaela Aubele , Axel Walch , Eva Gross , Rudolf Napieralski , Shuo Zhao , Nancy Ahmed , Marion Kiechle , Ute Reuning , Julia Dorn , Fred Sweep , Viktor Magdolen EMAIL logo and Manfred Schmitt
Published/Copyright: July 28, 2017

Abstract

Triple-negative breast cancer (TNBC), lacking the steroid hormone receptors ER and PR and the oncoprotein HER2, is characterized by its aggressive pattern and insensitivity to endocrine and HER2-directed therapy. Human kallikrein-related peptidases KLK1-15 provide a rich source of serine protease-type biomarkers associated with tumor growth and cancer progression for a variety of malignant diseases. In this study, recombinant KLK4 protein was generated and affinity-purified KLK4-directed polyclonal antibody pAb587 established to allow localization of KLK4 protein expression in tumor cell lines and archived formalin-fixed, paraffin-embedded TNBC tumor tissue specimens. For this, KLK4 protein expression was assessed by immunohistochemistry in primary tumor tissue sections (tissue microarrays) of 188 TNBC patients, mainly treated with anthracycline- or CMF-based polychemotherapy. KLK4 protein is localized in the cytoplasm of tumor and stroma cells. In this patient cohort, elevated stroma cell KLK4 expression, but not tumor cell KLK4 expression, is predictive for poor disease-free survival by univariate analysis (hazard ratio: 2.26, p=0.001) and multivariable analysis (hazard ratio: 2.12, p<0.01). Likewise, univariate analysis revealed a trend for statistical significance of elevated KLK4 stroma cell expression for overall survival of TNBC patients as well.

Acknowledgments

This project was supported by the Wilhelm Sander-Stiftung, Munich, Germany, contract number 2012.028.1 to M.A. and M.S. and 2016.024.1 to M.A., A.W., V.M. and M.S. as well as by the German Research Foundation (DFG), contract number DO 1772/1-1 to J.D.

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Received: 2017-3-2
Accepted: 2017-4-12
Published Online: 2017-7-28
Published in Print: 2017-9-26

©2017 Walter de Gruyter GmbH, Berlin/Boston

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