{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T04:55:12Z","timestamp":1777006512270,"version":"3.51.4"},"reference-count":109,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T00:00:00Z","timestamp":1775779200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Upper tract urothelial carcinoma (UTUC) is a relatively rare malignancy, far less frequent than its counterpart in the bladder, but with a more aggressive course, worse prognosis and unique diagnostic challenges. Despite the histological and molecular similarities between upper and lower tract urothelial tumours, UTUC has many key distinct traits, both clinical and genomic, and must be viewed as a separate entity from bladder urothelial carcinoma (BUC). Ureteroscopy with biopsy is the only means to obtain tissue for histo-logical confirmation of diagnosis and more accurate tumour grading, but is not always feasible or preferable because it carries the risk of potentially severe complications. Aside from the widely available but poorly sensitive urine cytology, a large variety of urine-based diagnostics are increasingly investigated as non-invasive alternatives to ureteroscopy. Fluorescence in situ hybridization (FISH) is the most widely used molecular assay for the diagnosis and monitoring of UTUC, but has failed, as of yet, to display a comparable diagnostic accuracy to the existing gold standards of computed tomography urography (CTU) and ureteroscopy. We herein aimed to comprehensively review all published data on the performance of FISH for the detection of UTUC, in comparison to urine cytology and other assays, while further commenting on the existing challenges and future perspectives in the field of urine-based diagnostics. Across all studies (n = 29) which were included in this review, the sensitivity and specificity of FISH ranged from 36.8% to 100.0% (mean: 75.5%; median: 78.9%) and 34.4% to 100.0% (mean: 84.9%; median: 89.9%), respectively, in the overall patient population, while in the low- versus high-grade subgroups, the sensitivity of FISH ranged from 30.0% to 90.0% (mean: 55.6%; median: 60%) versus 50.0% to 100.0% (mean: 77.9%; median: 78.8%). Furthermore, FISH showed superi-or sensitivity and similar or lower specificity in comparison to cytology, in the over-whelming majority of studies, while Xpert\u00aeBC Detection showed the highest sensitivity values among all evaluated assays, reaching 100% even in the low-grade subgroup, albeit at the cost of a significantly reduced specificity. Despite the adequate overall sensitivity and specificity of FISH, its suboptimal performance in the detection of low-grade UTUC seems to preclude its use as a stand-alone screening test.<\/jats:p>","DOI":"10.3390\/ijms27083406","type":"journal-article","created":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T10:20:16Z","timestamp":1775816416000},"page":"3406","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Performance of Urine Fluorescence In Situ Hybridization for Diagnosis of Upper Tract Urothelial Carcinoma: A Comprehensive Review"],"prefix":"10.3390","volume":"27","author":[{"given":"Dimitra","family":"Grapsa","sequence":"first","affiliation":[{"name":"Cytopathology Laboratory, \u201cLaiko\u201d General Hospital of Athens, 11527 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4782-8369","authenticated-orcid":false,"given":"Marina","family":"Sassi","sequence":"additional","affiliation":[{"name":"Cytopathology Laboratory, \u201cLaiko\u201d General Hospital of Athens, 11527 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8123-2676","authenticated-orcid":false,"given":"Panagiota","family":"Mikou","sequence":"additional","affiliation":[{"name":"Cytopathology Laboratory, \u201cLaiko\u201d General Hospital of Athens, 11527 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1016\/j.eururo.2024.07.027","article-title":"European Association of Urology Guidelines on Non-muscle-invasive Bladder Cancer (TaT1 and Carcinoma In Situ)-A Summary of the 2024 Guidelines Update","volume":"86","author":"Gontero","year":"2024","journal-title":"Eur. 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