FOXP3/TLS; a prognostic marker in patients with bladder carcinoma without muscle invasion

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dc.authorid0000-0002-3386-2075
dc.contributor.authorBalcik, Onur Yazdan
dc.contributor.authorYilmaz, Fatih
dc.date.accessioned2026-01-24T12:31:19Z
dc.date.available2026-01-24T12:31:19Z
dc.date.issued2025
dc.departmentAlanya Alaaddin Keykubat Üniversitesi
dc.description.abstractObjective: Bladder carcinoma (BC) is a common type of cancer. Approximately 20% of BC patients have non-muscle invasive bladder cancer (NMIBC). Despite adequate BCG treatment, recurrence occurs in approximately 40% of the patients. There is no adequate prognostic marker for recurrence in a group of patients. Forkhead box P3 (FOXP3) is a regulatory T cell marker that sometimes exhibits anti- tumoral effects and can be used as a tumor marker. T-cell immunoglobulin and mucin domain 3 (TIM-3) is an immune checkpoint inhibitor of T cells. Tertiary lymphoid structures (TLS) increase malignancy and inflammation in non-lymphoid organs. Therefore, we aimed to evaluate the prognostic value of FOXP3, TIM-3, and TLS in patients with NMIBC. Methods: Patients with pathologically confirmed NMIBC were included in this study. Stromal and intraepithelial cells were evaluated separately using immunohistochemistry, and FOXP3, TIM-3, TLS, FOXP3/TLS, and TIM-3/TLS were calculated and noted. The cutoff value was determined using ROC analysis. Recurrence-free survival (RFS) and overall survival (OS) were evaluated using univariate and multivariate Cox proportional hazard analyses. Results: The study included ninety-six patients. FOXP3/TLS high group had a better RFS than FOXP3/TLS low group (P = 0.001; HR, 0.079; 95% CI, 0.019-0.337). This was also significant in the multivariate analysis (P = 0.018; HR, 0.125; 95% CI, 0.022-0.705). In the group receiving BCG, FOXP3/TLS, FOXP3-TLS, TIM-3-TLS and TIM-3/TLS elevation were lower in patients with relapse than in patients without relapse and were statistically significant. Combined TIM-3 and FOXP3 elevation was found to be good prognostic regardless of whether it was found in intraepithelial, stromal or TLS. Conclusion: FOXP3/TLS elevation is a good prognostic and predictive marker in all non-muscle invasive bladder cancer cases and in the subgroup receiving BCG. Elevation of FOXP3-TLS, TIM-3-TLS, and TIM-3/TLS is associated with longer RFS in patients receiving BCG. Combined TIM-3 and FOXP3 elevation is indicative of a low recurrence rate in NMIBC. (c) 2024 Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.
dc.description.sponsorshipInterdisciplinary Oncology Association (IDOD)
dc.description.sponsorshipThis study was financial supported by the Interdisciplinary Oncology Association (IDOD).
dc.identifier.doi10.1016/j.urolonc.2024.11.017
dc.identifier.endpage2.6799999999999999147E+28
dc.identifier.issn1078-1439
dc.identifier.issn1873-2496
dc.identifier.issue4
dc.identifier.pmid39668105
dc.identifier.scopus2-s2.0-85211716283
dc.identifier.scopusqualityQ1
dc.identifier.startpage2.68E+11
dc.identifier.urihttps://doi.org/10.1016/j.urolonc.2024.11.017
dc.identifier.urihttps://hdl.handle.net/20.500.12868/5808
dc.identifier.volume43
dc.identifier.wosWOS:001445229000001
dc.identifier.wosqualityQ2
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.language.isoen
dc.publisherElsevier Science Inc
dc.relation.ispartofUrologic Oncology-Seminars and Original Investigations
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/closedAccess
dc.snmzKA_WoS_20260121
dc.subjectFOXP3
dc.subjectTIM-3
dc.subjectTLS
dc.subjectRFS
dc.subjectTreg
dc.titleFOXP3/TLS; a prognostic marker in patients with bladder carcinoma without muscle invasion
dc.title.alternativea prognostic marker in patients with bladder carcinoma without muscle invasion
dc.typeArticle

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