Abstract
BackgroundUrinary 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 methodsWe 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.ResultsThe 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.ConclusionsUrinary Calprotectin cannot be regarded as a specific tumour marker for bladder cancer, but rather as a surrogate parameter for tumour inflammation.
Highlights
Bladder cancer (BC) is the most common malignancy of the male and female urinary system, with urothelial carcinoma being the predominant histologic type in developed countries [1]
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)
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)
Summary
Bladder cancer (BC) is the most common malignancy of the male and female urinary system, with urothelial carcinoma being the predominant histologic type in developed countries [1]. Research efforts were directed towards finding less invasive alternatives, such as biomarkers, that reflect the presence of urothelial carcinoma, which is considered an indicator for a high risk of both low-grade and high-grade tumours. Proteomic studies in blood serum of patients with BC revealed Calprotectin–the heterodimer of the proteins S100A8 and S100A9 –as a tumour-associated protein that is linked to bladder wall muscle invasion of the tumour as well as cancer-specific survival [3,4]. Since neutrophils associated to urinary tract infections may release Calprotectin, Ebbing et al [7] identified uC as a potential biomarker for BC under the exclusion of urinary tract infections. Our aim was to investigate the association between sterile leukocyturia and urinary Calprotectin in low-grade and high-grade bladder cancer
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