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

Authors

Enes Altın, Çağrı Doğan, Ayşegül İsal Arslan, Erdem Can Topkaç, Cenk Murat Yazıcı, Rıdvan Özcan, Hacı Murat Akgül, Mehmet Fatih Şahin

Published in

BMC cancer. Jun 20, 2026. Epub Jun 20, 2026.

Abstract

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.
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.
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]).
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.

PMID:
42321663
Bibliographic data and abstract were imported from PubMed on 20 Jun 2026.

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