A New Marker for Prediction of Recurrence in Low-Risk Bladder Cancer: Retrospective Study of ELF-3 and TSC-1

Objective: Tumor recurrence remains a major clinical challenge among patients with low-risk non-muscle invasive bladder cancer (NMIBC). Molecular studies have identified two main subtypes with distinct genetic pathways: papillary, low-grade tumors often associated with FGFR3 mutations and favorable outcomes, and nonpapillary, high-grade tumors characterized by high progression and muscle invasion rates. This study aims to evaluate the predictive value of immunohistochemical (IHC) markers—CD44, CK5/6, CK20, GATA3 , Cerb-B2, ELF-3, and TSC-1—for recurrence in patients with low-risk NMIBC. Materials and Methods: This retrospective study included 40 patients with NMIBC selected from 320 individuals who underwent transurethral resection of bladder tumors (TUR-BT) between 2011 and 2019. Patients were categorized into recurrence ( n = 20) and nonrecurrence ( n = 20) groups. Tissues were reevaluated and stained for CK4, CK5/6, CK20, CD44, GATA3 , Cerb-B2, ELF-3, and TSC-1 using IHC methods. Associations between clinicopathological variables and recurrence were statistically analyzed. Results: Recurrence correlated significantly with tumor number ( p = 0.036 ), while age, sex, smoking status, and tumor size showed no significant association ( p > 0.05). CD44 positivity was predominantly observed in nonrecurrent cases ( p = 0.022 ), whereas TSC-1 positivity was strongly associated with recurrence ( p = 0.003 ). Multivariate regression revealed that CD44 positivity reduced the recurrence risk (OR = 0.142), while TSC-1 positivity increased it more than 21-fold (OR = 21.871). Tumors located at the ureteral orifice exhibited a lower recurrence risk (OR = 0.098). Conclusion: This study indicates that low CD44 expression and high TSC-1 expression in patients with low-risk NMIBC may serve as predictors of tumor recurrence. Assessment of these markers could enable earlier identification of patients at increased risk, thereby facilitating strict surveillance and timely management of treatment strategies.