Local cytokine concentration in patients with non-muscle invasive bladder cancer of low malignant potential and with varying rates of recurrence

Aim. To investigate local concentrations and distribution of cytokines in tumor tissue and perifocal zone in non-muscle invasive bladder cancer of low malignant potential in patients with low and high probability of disease recurrence.

 Materials and methods. We have studied tumor and perifocal zone fragments of 31 patients with verified non-muscle invasive bladder cancer of low malignant potential and with different probabilities of recurrence. Fifteen (15) patients developed recurrences 6–9 months after combination treatment. The fragments of primary and recurrent tumors were  echanically disaggregated and centrifuged at 1500 rpm for 10 minutes. Levels of cytokines interleukin (IL) -1β, -6, -8, -10, -18, tumor necrosis factor α (TNF-α), interferon-γ (Vektor-Best, Russia), and epithelial neutrophil activating peptide 78 (ENA-78) (CXCL-5 chemokine) (Cloud-Clone Corp., USA) were measured in the samples by ELISA. Results were statistically processed using Statistica 13 software (StatSoft Inc., USA), and presented as median and interquartile range – 25th and 75th percentile (Ме [LQ; UQ]).

Results. Comparison of cytokine concentrations within the groups showed that the levels of inflammatory cytokines (TNF-α, IL-1β, IL-8, IL-6, IL-18) in tumor tissues were higher than in the perifocal zone tissues. This pattern was expected because tumor is the main site of inflammation. Comparison of these indicators between groups showed that in tumor tissues with an unfavorable course of the disease, namely disease recurrence, the levels of almost all inflammatory cytokines (TNF-α, IL-1β, IL-8, IL-6) were higher. A similar pattern was observed when comparing the levels of cytokines in the tissues of the perifocal zone. These differences were statistically significant. ENA-78 concentration was not determined in all cases.

Conclusion. The data obtained during the study indicates that in patients with unfavorable disease course (recurrence), tumor growth is associated with high expression of proinflammatory cytokines, which can subsequently lead to development of disease recurrence.

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