The prognostic and clinicopathological significance of Tim-3 and PD-1 expression in the prognosis of upper urinary tract urothelial carcinoma

Abstract

ObjectiveUpper urinary tract urothelial carcinoma (UTUC) is a relatively uncommon disease with few reported molecular markers. This study evaluated Tim-3 and PD-1 expression in primary UTUC and its impact on patients' clinical outcomes. MethodsTim-3 and PD-1 protein expression was detected by immunohistochemistry in paraffin-embedded sections from 101 UTUC patients. The H-score was correlated with clinicopathologic outcomes and the long-term recurrence and survival rates. ResultsT cell immunoglobulin mucin-3 (Tim-3) protein was overexpressed in UTUC cells, especially tumour-infiltrating lymphocytes (TILs) and endothelial cells. We found that 95% (95/101) of UTUC tissues had dysregulated Tim-3 expression, of which 44% (44/101) showed high expression. High Tim-3 expression (H-score≥100) was significantly correlated with advanced pathological grade, advanced T stage and tumour recurrence (P=0.016, 0.001 and < 0.001, respectively) and with poor intravesical recurrence-free survival (IRFS) and overall survival (OS) (P< 0.001 and 0.003). Moreover, another immune checkpoint molecule, programmed death receptor-1 (PD-1), was also assessed in our study. Among patients in the low Tim-3 expression subgroup, those with high PD-1 expression experienced intravesical recurrence (IVR) more often than those with low PD-1 expression (P< 0.001). However, the PD-1 expression level had no effect on prognosis in the high Tim-3 expression subgroup. ConclusionWe confirmed that high Tim-3 protein expression can be used as an indicator of earlier IVR and shorter OS in patients with UTUC, while high expression of PD-1 is only related to earlier IVR. We showed that Tim-3 plays a more important role in tumour recurrence and progression than PD-1. Collectively, our findings support the use of Tim-3 and PD-1 as clinical prognostic factors indicating poor patient survival. Tim-3, alone or in combination with PD-1, could become a target for future UTUC therapies, but further prospective studies are needed.