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Relevance of cellular and serum carbonic anhydrase IX in primary breast cancer

Journal of Cancer Research and Clinical Oncology volume 139, pages 747–754 (2013)Cite this article

Abstract

Background

Carbonic anhydrase IX (CAIX) is involved in pH homeostasis, growth and survival of tumor cells. Besides the membranous form of CAIX, a soluble form is detectable in serum (s-CAIX). Overexpression of CAIX in tumors offers the opportunity for therapeutic strategies such as CAIX targeting antibodies. The aim of this study was to examine the relationships of CAIX mRNA expression and s-CAIX levels with clinicopathological parameters and survival of patients with primary breast cancer.

Methods

Tumor tissue of 169 primary breast cancer patients was analyzed for RNA expression by microarray analysis (Affymetrix HG-U133A). Concentration of s-CAIX was determined by ELISA in blood samples of 140 patients.

Results

In tumor tissue, CAIX mRNA signal intensities (MAS5 values) ranged from 34 to 2,513. Higher CAIX expression was associated with younger age (</≥50 years p = 0.040), negative hormone receptors (estrogen receptor p = 0.004; progesterone receptor p = 0.022) and positive nodal status (p = 0.001) as well as with shorter disease-free survival (p = 0.031). Concentrations of s-CAIX ranged from 56 to 1,500 pg/ml. There was no correlation between s-CAIX and CAIX mRNA levels as well as clinicopathological characteristics or outcome.

Conclusion

In contrast to reported immunohistochemical studies, we performed RNA-based tissue analyses of CAIX expression and, for the first time, analyzed CAIX serum levels in primary breast cancer. The correlations between CAIX RNA expression and prognostic factors and patient outcome support a biologic role of CAIX in early breast cancer. A role of s-CAIX in primary breast cancer is not supported by our findings.

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Acknowledgments

We thank Katrin Beck and Maila Rossberg for excellent technical assistance.

Conflict of interest

All authors declare no competing interests. ELISA kits were provided at no cost by Oncogene Science, a former part of Siemens Medical Solutions Diagnostics and now part of Wilex. The company did not have a role in study design or collection, analysis and interpretation of data nor in the writing of the manuscript.

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Affiliations

  1. Department of Gynecology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246, Hamburg, Germany

    Dina Schütze, Karin Milde-Langosch, Isabell Witzel, Fritz Jänicke & Volkmar Müller

  2. Department of Obstetrics and Gynecology, University Medical Center Lübeck, Lübeck, Germany

    Achim Rody

  3. Department of Obstetrics and Gynecology, University Medical Center Frankfurt, Frankfurt, Germany

    Thomas Karn

  4. Department of Obstetrics and Gynecology, University Medical Center Mainz, Mainz, Germany

    Marcus Schmidt

  5. Department of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

    Matthias Choschzick

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  1. Dina Schütze
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  2. Karin Milde-Langosch
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  7. Matthias Choschzick
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  8. Fritz Jänicke
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  9. Volkmar Müller
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Correspondence to Volkmar Müller.

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Schütze, D., Milde-Langosch, K., Witzel, I. et al. Relevance of cellular and serum carbonic anhydrase IX in primary breast cancer. J Cancer Res Clin Oncol 139, 747–754 (2013). https://doi.org/10.1007/s00432-013-1378-4

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  • DOI: https://doi.org/10.1007/s00432-013-1378-4

Keywords

  • Carbonic anhydrase IX
  • RNA expression
  • Serum isoform
  • Primary breast cancer