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Urinary calprotectin: a new diagnostic marker in urothelial carcinoma of the bladder

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Abstract

Purpose

Recently, a proteomic study of sera from patients with bladder cancer identified S100A8 and S100A9 as tumor-associated proteins. The present cross-sectional study investigates whether calprotectin, the heterodimer of S100A8/S100A9 may serve as a urinary biomarker for the detection of urothelial bladder cancer.

Methods

Urinary calprotectin concentrations were assessed in a population of 181 subjects including 46 cases of bladder cancer. 41 cases of renal cell cancer, 54 cases of prostate cancer, and 40 healthy subjects served as control. Acute kidney injury, urinary tract infection, previous BCG-treatment and secondary transurethral resection of the bladder tumor were defined as exclusion criteria. Assessment was performed by enzyme-linked immunosorbent assay and immunohistochemistry detecting calprotectin.

Results

Median calprotectin concentrations (ng/ml) were significantly higher in patients with bladder cancer than in healthy controls (522.3 vs. 51.0, p < 0.001), renal cell cancer (90.4, p < 0.001), and prostate cancer (71.8, p < 0.001). In urothelial carcinoma prominent immunostaining occurred in a subset of tumor cells and in infiltrating myeloid cells. Receiver operating characteristic analysis provided an area under the curve of 0.88 for the differentiation of bladder cancer and healthy control. A cut-off value of 140 ng/ml (determined by Youden’s index) resulted in sensitivity and specificity values of 80.4 and 92.5 %. Low grade tumors were associated with significantly lower calprotectin concentrations than high grade tumors (351.9 vs. 1635.2 ng/ml, p = 0.004).

Conclusions

Urothelial malignancies are associated with highly increased concentrations of calprotecin in the urine. In absence of renal failure and pyuria, calprotectin constitutes a promising biomarker for the detection of bladder cancer.

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Acknowledgments

We thank Simone Voigt and Silvia Heinze for their indefatigable efforts in this study. The study was funded by the German Research Foundation (Research Unit FOR1368).

Conflict of interest

None.

Author information

Authors and Affiliations

  1. Department of Urology, Charité, Campus Benjamin Franklin, Berlin, Germany

    Jan Ebbing, Karsten Günzel, Carsten Kempkensteffen & Kurt Miller

  2. Department of Nephrology, Charité, Campus Mitte, Berlin, Germany

    Susanne Mathia & Christian Rosenberger

  3. Department of Nephrology, Charité, Campus Benjamin Franklin, Berlin, Germany

    Felix S. Seibert, Nikolaos Pagonas, Frederic Bauer, Walter Zidek & Timm H. Westhoff

  4. Medizinische Klinik I, Universitätsklinik Marienhospital Herne, Ruhr University of Bochum, Hölkeskampring 40, 44625, Herne, Germany

    Felix S. Seibert, Nikolaos Pagonas, Frederic Bauer & Timm H. Westhoff

  5. Department of Pathology, Charité, Campus Mitte, Berlin, Germany

    Ergin Kilic & Kurt Miller

  6. Department of Urology, Charité, Campus Mitte, Berlin, Germany

    Barbara Erber

  7. Department of Urology, Universitätsspital Basel, Basel, Switzerland

    Jan Ebbing & Alexander Bachmann

Authors
  1. Jan Ebbing
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  2. Susanne Mathia
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  3. Felix S. Seibert
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  7. Karsten Günzel
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  8. Ergin Kilic
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  9. Carsten Kempkensteffen
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  11. Alexander Bachmann
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  12. Christian Rosenberger
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  13. Walter Zidek
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  14. Timm H. Westhoff
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Corresponding author

Correspondence to Timm H. Westhoff.

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Ebbing, J., Mathia, S., Seibert, F.S. et al. Urinary calprotectin: a new diagnostic marker in urothelial carcinoma of the bladder. World J Urol 32, 1485–1492 (2014). https://doi.org/10.1007/s00345-013-1227-8

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  • DOI: https://doi.org/10.1007/s00345-013-1227-8

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