{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T13:08:24Z","timestamp":1789391304724,"version":"build-2803163510"},"reference-count":37,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T00:00:00Z","timestamp":1789344000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"University of Medicine and Pharmacy \u201cIuliu Hatieganu\u201d Cluj Napoca","award":["1032\/69\/13.01.2021"],"award-info":[{"award-number":["1032\/69\/13.01.2021"]}]},{"award":["1032\/69\/13.01.2021"],"award-info":[{"award-number":["1032\/69\/13.01.2021"]}],"id":[{"id":"https:\/\/ror.org\/051h0cw83","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Clin. Med.","JCM"],"abstract":"<jats:p>Background: Urinary cytology is routinely used as an adjunct to cystoscopy in the diagnosis and surveillance of urothelial carcinoma. Although it has high specificity for high-grade tumors, its sensitivity for low-grade papillary lesions is limited. Activating mutations in the fibroblast growth factor receptor 3 (FGFR3) gene are frequently encountered in non-muscle-invasive bladder cancer and may provide a complementary molecular method for detecting tumors that are not identified by conventional cytology. Objective: To compare conventional urinary cytology with urinary detection of the FGFR3 hotspot mutations S249C and R248C in patients undergoing evaluation for urothelial carcinoma. Materials and Methods: This single-center prospective pilot study included adult patients with clinically and radiologically confirmed bladder tumors evaluated between February 2022 and December 2023. Voided urine specimens were collected before cystoscopy or urinary tract instrumentation. Urine cytology was performed after centrifugation, conventional smear preparation, alcohol fixation, and Papanicolaou staining, with interpretation according to The Paris System for Reporting Urinary Cytology. DNA extracted from paired urine specimens was analyzed for the FGFR3 S249C and R248C hotspot mutations using TaqMan mutation-detection assays and real-time polymerase chain reaction. Histopathological examination of transurethral resection, bladder biopsy, or radical surgical specimens served as the reference standard. Results: Twenty-six patients were included, with a mean age of 69.2 \u00b1 11.5 years; 24 patients (92.3%) were male. At least one FGFR3 mutation was detected in 17 patients (65.4%), whereas nine patients (34.6%) had no detectable mutation. The S249C mutation was identified in three patients, while the R248C mutation was detected in nine patients, 5 patients were positive for both mutations.<\/jats:p>","DOI":"10.3390\/jcm15187117","type":"journal-article","created":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T12:09:51Z","timestamp":1789387791000},"page":"7117","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Paired Urinary Cytology and Targeted FGFR3 S249C\/R248C Mutation Detection in Urine from Patients with Bladder Cancer: A Pilot Study"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-6793-0016","authenticated-orcid":false,"given":"Bogdan-Petru","family":"Tichil","sequence":"first","affiliation":[{"name":"Department of Cell and Molecular Biology, Faculty of Medicine, University of Medicine and Pharmacy \u201cIuliu Hatieganu\u201d, 400349 Cluj-Napoca, Romania"},{"name":"Deva Emergency County Hospital, 330084 Deva, Romania"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8504-8032","authenticated-orcid":false,"given":"Anamaria","family":"Besleaga","sequence":"additional","affiliation":[{"name":"Deva Emergency County Hospital, 330084 Deva, Romania"},{"name":"Department of Otorhinolaryngology, University of Medicine and Pharmacy \u201cIuliu Hatieganu\u201d, 400349 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7779-3147","authenticated-orcid":false,"given":"Ioana","family":"Gheorghiu","sequence":"additional","affiliation":[{"name":"Department of Medical Informatics and Biostatistics, University of Medicine and Pharmacy \u201cIuliu Hatieganu\u201d, 400349 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"}]},{"given":"Alin-Dan","family":"Chiorean","sequence":"additional","affiliation":[{"name":"Department of Cell and Molecular Biology, Faculty of Medicine, University of Medicine and Pharmacy \u201cIuliu Hatieganu\u201d, 400349 Cluj-Napoca, Romania"},{"name":"Clinical Institute of Urology and Renal Transplant, 400000 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0811-0821","authenticated-orcid":false,"given":"Mihaela Laura","family":"Vica Matei","sequence":"additional","affiliation":[{"name":"Department of Cell and Molecular Biology, Faculty of Medicine, University of Medicine and Pharmacy \u201cIuliu Hatieganu\u201d, 400349 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0898-7626","authenticated-orcid":false,"given":"Adrian","family":"Florea","sequence":"additional","affiliation":[{"name":"Department of Cell and Molecular Biology, Faculty of Medicine, University of Medicine and Pharmacy \u201cIuliu Hatieganu\u201d, 400349 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Yang, Z., Song, F., and Zhong, J. (2025). Urinary biomarkers in bladder cancer: FDA-approved tests and emerging tools for diagnosis and surveillance. Cancers, 17.","DOI":"10.20944\/preprints202510.0625.v1"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Gontero, P., Mariappan, P., Pradere, B., Rai, B.P., Liedberg, F., Comp\u00e9rat, E., Teoh, J.Y., Moschini, M., Soria, F., and van Rhijn, B.W.G. (2026). EAU Guidelines on Non-Muscle-Invasive Bladder Cancer (TaT1 and CIS)\u2014A Summary of the 2026 Guidelines Update. Eur. Urol., advance online publication.","DOI":"10.1016\/j.eururo.2026.04.009"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1097\/JU.0000000000003846","article-title":"Diagnosis and treatment of non-muscle invasive bladder cancer: AUA\/SUO guideline: 2024 amendment","volume":"211","author":"Holzbeierlein","year":"2024","journal-title":"J. Urol."},{"key":"ref_4","unstructured":"National Comprehensive Cancer Network (2026). NCCN Clinical Practice Guidelines in Oncology: Bladder Cancer, National Comprehensive Cancer Network. Version 2.2026."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Matuszczak, M., and Salagierski, M. (2020). Diagnostic and prognostic potential of biomarkers CYFRA 21.1, ERCC1, p53, FGFR3 and TATI in bladder cancers. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21093360"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Batista, R., Vinagre, J., Prazeres, H., Sampaio, C., Peralta, P., Concei\u00e7\u00e3o, P., Sismeiro, A., Le\u00e3o, R., Gomes, A., and Furriel, F. (2019). Validation of a novel, sensitive, and specific urine-based test for recurrence surveillance of patients with non-muscle-invasive bladder cancer in a comprehensive multicenter study. Front. Genet., 10.","DOI":"10.3389\/fgene.2019.01237"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1111\/bju.15137","article-title":"A systematic review on mutation markers for bladder cancer diagnosis in urine","volume":"127","author":"Hentschel","year":"2021","journal-title":"BJU Int."},{"key":"ref_8","first-page":"412","article-title":"Urine cytology and adjunct markers for detection and surveillance of bladder cancer","volume":"2","author":"Sullivan","year":"2010","journal-title":"Am. J. Transl. Res."},{"key":"ref_9","first-page":"207","article-title":"Urine and bladder washing cytology for detection of urothelial carcinoma: Standard test with new possibilities","volume":"44","year":"2010","journal-title":"Radiol. Oncol."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Bisharah, S., Raap, M., and Abbas, M. (2025). Urine cytological diagnostics: Possibilities and limitations\u2014A 25-year review and overview at Hannover Medical School. Clin. Pract., 15.","DOI":"10.3390\/clinpract15120234"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"922","DOI":"10.7326\/M15-0997","article-title":"Urinary biomarkers for diagnosis of bladder cancer: A systematic review and meta-analysis","volume":"163","author":"Chou","year":"2015","journal-title":"Ann. Intern. Med."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Nikas, I.P., Seide, S., Proctor, T., Kleinaki, Z., Kleinaki, M., and Reynolds, J.P. (2022). The Paris System for Reporting Urinary Cytology: A meta-analysis. J. Pers. Med., 12.","DOI":"10.3390\/jpm12020170"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"73","DOI":"10.4274\/uob.galenos.2024.2024.3.3","article-title":"Contemporary role of urine cytology in bladder cancer","volume":"23","author":"Kars","year":"2024","journal-title":"Bull. Urooncol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"328","DOI":"10.30699\/ijp.2022.548036.2833","article-title":"Accuracy of Paris 2016 System for non-invasive diagnosis bladder malignancy","volume":"17","author":"Rakhshan","year":"2022","journal-title":"Iran. J. Pathol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1159\/000521139","article-title":"Application of the Paris Reporting System for urine cytology: The three-year experience of a single tertiary care institute in Thailand","volume":"66","author":"Phruttinarakorn","year":"2022","journal-title":"Acta Cytol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1111\/his.70038","article-title":"The Paris System for reporting urinary cytology: What worked and what still needs to be improved","volume":"88","author":"Wojcik","year":"2026","journal-title":"Histopathology"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"17","DOI":"10.4103\/cytojournal.cytojournal_12_17","article-title":"Interobserver reproducibility of The Paris System for Reporting Urinary Cytology","volume":"14","author":"Long","year":"2017","journal-title":"CytoJournal"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Yamasaki, M., Taoka, R., Katakura, K., Matsunaga, T., Kani, N., Honda, T., Harada, S., Tohi, Y., Matsuoka, Y., and Kato, T. (2022). The Paris System for reporting urinary cytology improves the negative predictive value of high-grade urothelial carcinoma. BMC Urol., 22.","DOI":"10.1186\/s12894-022-01005-8"},{"key":"ref_19","first-page":"59","article-title":"The Paris System for Reporting Urinary Cytology: An updated review","volume":"3","author":"Chen","year":"2023","journal-title":"J. Clin. Transl. Pathol."},{"key":"ref_20","first-page":"505","article-title":"Urine cytology and axillary testing for interpretation and follow-up of urinary tumors","volume":"61","author":"Kalogeraki","year":"2022","journal-title":"Acta Clin. Croat."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3310\/hta14040","article-title":"Systematic review of the clinical effectiveness and cost-effectiveness of photodynamic diagnosis and urine biomarkers and cytology for the detection and follow-up of bladder cancer","volume":"14","author":"Mowatt","year":"2010","journal-title":"Health Technol. Assess."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"6554","DOI":"10.21037\/tcr-20-1990","article-title":"Review of non-invasive urinary biomarkers in bladder cancer","volume":"9","author":"Lee","year":"2020","journal-title":"Transl. Cancer Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"28","DOI":"10.18063\/cp.v3i1.302","article-title":"The role of FGFR3 in the diagnosis and treatment of bladder cancer: A review","volume":"3","author":"Wei","year":"2021","journal-title":"Cancer Plus"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Kompier, L.C., Lurkin, I., van der Aa, M.N.M., van Rhijn, B.W.G., van der Kwast, T.H., and Zwarthoff, E.C. (2010). FGFR3, HRAS, KRAS, NRAS and PIK3CA mutations in bladder cancer and their potential as biomarkers for surveillance and therapy. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0013821"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2001","DOI":"10.1007\/s00345-019-02779-7","article-title":"Mutations in CDKN2A and the FGFR3 genes on bladder cancer diagnosis: A systematic review and meta-analysis","volume":"37","author":"Reis","year":"2019","journal-title":"World J. Urol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"7743","DOI":"10.1158\/1078-0432.CCR-05-1045","article-title":"A simple and fast method for the simultaneous detection of nine fibroblast growth factor receptor 3 mutations in bladder cancer and voided urine","volume":"11","author":"Lurkin","year":"2005","journal-title":"Clin. Cancer Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1002\/cncr.11536","article-title":"Identification of fibroblast growth factor receptor 3 mutations in urine sediment DNA samples complements cytology in bladder tumor detection","volume":"98","author":"Mourtzinos","year":"2003","journal-title":"Cancer"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Yu, S.H., Kim, S.S., Kim, S., Lee, H., and Kang, T.W. (2024). FGFR3 mutations in urothelial carcinoma: A single-center study using next-generation sequencing. J. Clin. Med., 13.","DOI":"10.3390\/jcm13051305"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Roperch, J.P., and Hennion, C. (2020). A novel ultra-sensitive method for the detection of FGFR3 mutations in urine of bladder cancer patients\u2014Design of the Urodiag PCR kit for surveillance of NMIBC. BMC Med. Genet., 21.","DOI":"10.1186\/s12881-020-01050-w"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"3011","DOI":"10.1158\/1078-0432.CCR-09-3013","article-title":"Fibroblast growth factor receptor 3 mutation analysis on voided urine for surveillance of patients with low-grade non-muscle-invasive bladder cancer","volume":"16","author":"Zuiverloon","year":"2010","journal-title":"Clin. Cancer Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1771","DOI":"10.1111\/cas.14000","article-title":"Diagnostic potential of TERT promoter and FGFR3 mutations in urinary cell-free DNA in upper tract urothelial carcinoma","volume":"110","author":"Hayashi","year":"2019","journal-title":"Cancer Sci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/j.euros.2024.02.009","article-title":"A genomic urine assay for surveillance of patients with bladder cancer treated with radiotherapy","volume":"62","author":"Kooper","year":"2024","journal-title":"Eur. Urol. Open Sci."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2787","DOI":"10.21037\/tau-20-1327","article-title":"Trends in urine biomarker discovery for urothelial bladder cancer: DNA, RNA, or protein?","volume":"10","author":"Ward","year":"2021","journal-title":"Transl. Androl. Urol."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Oyaert, M., Van Praet, C., Delrue, C., and Speeckaert, M. (2025). Novel urinary biomarkers for the detection of bladder cancer. Cancers, 17.","DOI":"10.3390\/cancers17081283"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"18","DOI":"10.3892\/ijo.2025.5724","article-title":"Unleashing the power of urine-based biomarkers in diagnosis, prognosis and monitoring of bladder cancer","volume":"66","author":"Wan","year":"2025","journal-title":"Int. J. Oncol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"10914","DOI":"10.1038\/s41467-024-55331-6","article-title":"AI allows pre-screening of FGFR3 mutational status using routine histology slides of muscle-invasive bladder cancer","volume":"15","author":"Bannier","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"830","DOI":"10.1200\/JCO.2026.44.7_suppl.830","article-title":"Detecting FGFR3 genomic alterations in liquid biopsies from patients with clinically advanced urothelial bladder cancer","volume":"44","author":"Basin","year":"2026","journal-title":"J. Clin. Oncol."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/15\/18\/7117\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T12:51:21Z","timestamp":1789390281000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/15\/18\/7117"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,14]]},"references-count":37,"journal-issue":{"issue":"18","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["jcm15187117"],"URL":"https:\/\/doi.org\/10.3390\/jcm15187117","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,14]]}}}