Prognostic Implication of Urothelial Stem Cell Markers Differs According to Primary Tumour Location in Non-Muscle-Invasive Bladder Cancer

Background/Aims: This study aimed to validate the value of urothelial stem cell (USC) markers ΔNp63, integrin β4, CD47, and CD44v6 in predicting the prognosis of non-muscle invasive bladder cancer (NMIBC) located in different anatomic regions of bladder. Methods: The study reviewed the clinicopathologic data of 169 patients with NMIBC. Using real-time PCR and immunohistochemistry, the expression of ΔNp63, integrin β4, CD47, and CD44v6 in archived specimens of patients with NMIBC were validated. Kaplan–Meier analysis and Cox proportional hazards model were used to assess the prognostic impact of USC markers for recurrent-free survival (RFS). Results: The Real-time PCR data showed that the expression of USC markers were higher in tumors located in the trigone and posterior wall than that in other regions of bladder (P< 0.05). Statistical analysis showed that high expression of ΔNp63 was correlated with tumor stage (P=0.023) and tumor size (P=0.001), that high expression of integrin β4 was correlated with tumor stage (P=0.026), tumor grade (P=0.005) and tumor size (P=0.003), and that high integrin β4, CD47, and CD44v6 expression were significantly associated with tumor recurrence (P=0.032, P=0.010, and P=0.043, respectively). Moreover, high expression of ΔNp63 and integrin β4 was correlated with poor RFS in patients with tumors located in the trigone (P=0.025 and P=0.023, respectively). High expression of integrin β4, CD47, and CD44v6 was correlated with poor RFS in patients with tumors in the posterior wall (P=0.017, P=0.033 and P=0.047, respectively). High expression of integrin β4 and CD47 was correlated with poor RFS in patients with tumors in the trigone/posterior wall area (P=0.002 and P=0.005, respectively). Conclusion: Our results suggest that USC markers are linked with poor prognosis of NMIBC patients, especially in patients with tumors in the trigone and posterior wall