Urinary Calprotectin loses specificity as tumour marker due to sterile leukocyturia associated with bladder cancer

PLoS One. 2019 Mar 14;14(3):e0213549. doi: 10.1371/journal.pone.0213549. eCollection 2019.

Abstract

Background: Urinary Calprotectin, a mediator of the innate immune system, has been identified as a biomarker in bladder cancer. Our aim was to investigate the association between sterile leukocyturia and urinary Calprotectin in low-grade and high-grade bladder cancer.

Materials and methods: We performed a prospective cross-sectional study including 52 patients with bladder cancer and 40 healthy controls. Definition of sterile leukocyturia was > 5.0 leukocytes per visual field in absence of bacteriuria.

Results: The rate of sterile leukocyturia in low-grade (60.0%) and high-grade (62.0%) bladder cancer was comparable (p = 0.87). However, the median absolute urinary leukocyte count in patients with sterile leukocyturia was significantly higher in high-grade than in low-grade bladder cancer (p < 0.01). Spearman correlation revealed a significant correlation between urinary Calprotectin and leucocyte concentration (R = 0.4, p < 0.001). Median urinary Calprotectin concentration was 4.5 times higher in bladder cancer patients with than in patients without sterile leukocyturia (p = 0.03). Subgroup analysis revealed a significant difference in urinary Calprotectin regarding the presence of sterile leukocyturia in high-grade patients (596.8 [91.8-1655.5] vs. 90.4 [28.0-202.3] ng ml-1, p = 0.02). Multivariate analysis identified the leukocyte concentration to be the only significant impact factor for urinary Calprotectin (OR 3.2, 95% CI 2.5-3.8, p = 0.001). Immunohistochemistry showed Calprotectin positive neutrophils and tumour cells in high-grade bladder cancer with sterile leukocyturia.

Conclusions: Urinary Calprotectin cannot be regarded as a specific tumour marker for bladder cancer, but rather as a surrogate parameter for tumour inflammation.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / urine*
  • Cross-Sectional Studies
  • Female
  • Humans
  • Leukocyte L1 Antigen Complex / urine*
  • Leukocytes / metabolism*
  • Leukocytes / pathology
  • Male
  • Middle Aged
  • Prospective Studies
  • Urinary Bladder Neoplasms / pathology
  • Urinary Bladder Neoplasms / urine*

Substances

  • Biomarkers, Tumor
  • Leukocyte L1 Antigen Complex

Grants and funding

This work was supported by the Krebsliga Beider Basel grant no. 11-2015 to JE. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.