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Objective <p>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.</p> Materials and methods <p>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 (<i>n</i> = 20), defined as tumor recurrence following TUR-BT, and nonrecurrence (<i>n</i> = 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.</p> Results <p>Recurrence was significantly correlated with tumor number (<i>p</i> = 0.036), whereas age, sex, smoking status, and tumor size showed no significant association (<i>p</i> &gt; 0.05). CD44 positivity was predominantly observed in nonrecurrent cases (<i>p</i> = 0.022), whereas TSC-1 positivity was strongly associated with recurrence (<i>p</i> = 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]).</p> Conclusion <p>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.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年6月20日

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

摘要

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.