ELF-3 and TSC-1 as potential markers of recurrence in low-risk non–muscle-invasive bladder cancer

Objective Tumor recurrence is a major clinical challenge in low-risk non-muscle invasive bladder cancer (NMIBC). Molecular studies have identified two main subtypes with distinct genetic pathways: papillary, low-grade tumors, often with FGFR3 mutations and favorable outcomes, and nonpapillary, high-grade tumors, which are linked to higher rates of progression and muscle invasion. This study evaluates the prognostic value of immunohistochemical (IHC) markers- cluster of differentiation 44 (CD44), cytokeratin 5/6 (CK5/6), cytokeratin 20 (CK20), GATA-binding protein 3 (GATA3), human epidermal growth factor receptor 2 (Cerb-B2), E74-like factor 3 (ELF-3), and tuberous sclerosis complex 1 (TSC-1)-for recurrence in patients with low-risk NMIBC.Materials and methods This retrospective study evaluated 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 two groups: recurrence (n = 20), defined as tumor recurrence following TUR-BT, and nonrecurrence (n = 20), those with no recurrence during follow-up. Tissues were reevaluated and stained for the following markers using IHC methods: CK5/6, CK20, CD44, GATA3, Cerb-B2, ELF-3, and TSC-1. Statistical analysis was performed to assess associations between clinicopathological variables and recurrence.Results Recurrence was significantly correlated with tumor number (p = 0.036), whereas 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). ELF-3 expression was uniformly positive in all cases and did not predict recurrence. Multivariate regression revealed that CD44 positivity reduced the recurrence risk (OR = 0.142, 95% CI: [0.028-0.714]), while TSC-1 positivity increased it more than 21-fold (OR = 21.871, 95% CI: [2.125-115.15]). Tumors located at the ureteral orifice were associated with increased recurrence risk (OR = 10.231, 95% CI: [1.121-93.341]).Conclusion This study suggests that low CD44 expression and high TSC-1 expression in patients with low-risk NMIBC may serve as prognostic markers for tumor recurrence. Assessing these markers can facilitate earlier identification of at-risk patients, enabling strict surveillance and timely management of treatment strategies.