{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T16:12:48Z","timestamp":1792512768161,"version":"4.5.0"},"reference-count":96,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,12,12]],"date-time":"2025-12-12T00:00:00Z","timestamp":1765497600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,12,12]],"date-time":"2025-12-12T00:00:00Z","timestamp":1765497600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Histopathology"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:p>Significant progress has been achieved in elucidating the molecular underpinnings of bladder cancer initiation and progression. Translational research has identified mutations in chromatin\u2010modifying genes such as KMT2D and KDM6A, which facilitate colonization of larger regions of the urothelium. Subsequent mutations in TP53, PIK3CA, FGFR3 or RB1 drive malignant transformation. Advances in personalized oncology now integrate clinical, pathological and molecular classifications in bladder cancer, representing a paradigm shift in the management of locally advanced and metastatic disease. Alterations in FGFR3, commonly found in the luminal\u2010papillary molecular subtype associated with low response to immunotherapy, are the target of erdafitinib. Enfortumab vedotin, which targets Nectin\u20104 (expressed in &gt;95% of urothelial carcinomas), is approved for patients who progress after chemotherapy and\/or immunotherapy. Evidence suggests that Nectin\u20104 gene amplification may further refine patient stratification. Sacituzumab govitecan, an antibody\u2013drug conjugate directed against Trop\u20102, is effective in basal, luminal and stroma\u2010rich subtypes but not in neuroendocrine carcinomas. In addition, therapies developed for HER2\u2010positive breast cancer have shown efficacy in urothelial carcinoma, with recent data from the DESTINY pan\u2010tumour phase II trial leading to FDA approval of trastuzumab deruxtecan for HER2\u2010overexpressing metastatic urothelial carcinoma. This paper is a comprehensive review of the molecular pathology of bladder cancer, highlighting advances in molecular classification, biomarkers and personalized therapies. The transition from morphology\u2010based classifications to combined morphological and molecular approaches, with therapeutic implications, is also addressed.<\/jats:p>","DOI":"10.1111\/his.15555","type":"journal-article","created":{"date-parts":[[2025,12,12]],"date-time":"2025-12-12T13:23:30Z","timestamp":1765545810000},"page":"65-85","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Molecular pathology of bladder cancer"],"prefix":"10.1111","volume":"88","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3161-8164","authenticated-orcid":false,"given":"Antonio","family":"Lopez\u2010Beltran","sequence":"first","affiliation":[{"name":"Unit of Anatomic Pathology, Department of Morphological Sciences Cordoba University Medical School  Cordoba Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4360-4352","authenticated-orcid":false,"given":"Ana","family":"Blanca","sequence":"additional","affiliation":[{"name":"Unit of Anatomic Pathology, Department of Morphological Sciences Cordoba University Medical School  Cordoba Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4528-3724","authenticated-orcid":false,"given":"Michelle R.","family":"Downes","sequence":"additional","affiliation":[{"name":"Precision Diagnostics and Therapeutics Program, Department of Anatomic Pathology Sunnybrook Health Sciences Centre  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5981-3514","authenticated-orcid":false,"given":"Alessia","family":"Cimadamore","sequence":"additional","affiliation":[{"name":"Institute of Pathological Anatomy, Department of Medicine (DAME) Udine University  Udine Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3938-610X","authenticated-orcid":false,"given":"Rodolfo","family":"Montironi","sequence":"additional","affiliation":[{"name":"Molecular Medicine and Cell Therapy Foundation, Department of Clinical and Molecular Sciences Polytechnic University of the Marche Region  Ancona Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6049-5293","authenticated-orcid":false,"given":"Liang","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Brown University Warren Alpert Medical School Lifespan Academic Medical Center, and The Legorreta Cancer Center at Brown University  Providence Rhode Island USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,12,12]]},"reference":[{"key":"e_1_2_15_2_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21871"},{"key":"e_1_2_15_3_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj-2023-076743"},{"key":"e_1_2_15_4_1","volume-title":"Cancer today","author":"Ferlay J","year":"2024"},{"key":"e_1_2_15_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.humpath.2021.04.001"},{"key":"e_1_2_15_6_1","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0000000000002053"},{"key":"e_1_2_15_7_1","doi-asserted-by":"publisher","DOI":"10.3390\/jpm13050756"},{"key":"e_1_2_15_8_1","article-title":"Immune checkpoint inhibitors for the treatment of bladder cancer","volume":"13","author":"Lopez\u2010Beltran A","year":"2021","journal-title":"Cancer"},{"key":"e_1_2_15_9_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers14071795"},{"key":"e_1_2_15_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.path.2024.09.003"},{"key":"e_1_2_15_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cll.2023.08.010"},{"key":"e_1_2_15_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pathol.2023.10.016"},{"key":"e_1_2_15_13_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2023.1114203"},{"key":"e_1_2_15_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.urolonc.2019.04.010"},{"key":"e_1_2_15_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.humpath.2022.06.005"},{"key":"e_1_2_15_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41572-023-00468-9"},{"key":"e_1_2_15_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-55331-6"},{"key":"e_1_2_15_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pathol.2025.02.003"},{"key":"e_1_2_15_19_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.23.02005"},{"key":"e_1_2_15_20_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.986598"},{"issue":"5","key":"e_1_2_15_21_1","article-title":"PD14\u201005 the stroma\u2010rich consensus bladder cancer subtype correlates with improved prognosis after neoadjuvant immunotherapy and radical cystectomy","volume":"211","author":"Jong JJ","year":"2024","journal-title":"J. Urol."},{"key":"e_1_2_15_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2021.03.014"},{"key":"e_1_2_15_23_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.23.01983"},{"key":"e_1_2_15_24_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.abe0955"},{"key":"e_1_2_15_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11033-023-08689-7"},{"key":"e_1_2_15_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41585-023-00847-7"},{"key":"e_1_2_15_27_1","doi-asserted-by":"publisher","DOI":"10.1158\/1541-7786.MCR-20-0751"},{"key":"e_1_2_15_28_1","doi-asserted-by":"publisher","DOI":"10.1242\/dmm.008888"},{"key":"e_1_2_15_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc3817"},{"key":"e_1_2_15_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature12965"},{"key":"e_1_2_15_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2017.05.032"},{"key":"e_1_2_15_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2016.05.004"},{"key":"e_1_2_15_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2019.09.006"},{"key":"e_1_2_15_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2020.06.048"},{"key":"e_1_2_15_35_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-20-0977"},{"key":"e_1_2_15_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.09.007"},{"key":"e_1_2_15_37_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers13215500"},{"key":"e_1_2_15_38_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers15072149"},{"key":"e_1_2_15_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.humpath.2020.01.004"},{"key":"e_1_2_15_40_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00428-019-02593-x"},{"key":"e_1_2_15_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2016.08.036"},{"key":"e_1_2_15_42_1","doi-asserted-by":"publisher","DOI":"10.1111\/his.13063"},{"key":"e_1_2_15_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2014.01.009"},{"key":"e_1_2_15_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.humpath.2020.09.010"},{"key":"e_1_2_15_45_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00428-019-02618-5"},{"key":"e_1_2_15_46_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00428-017-2190-3"},{"key":"e_1_2_15_47_1","doi-asserted-by":"publisher","DOI":"10.1002\/path.4886"},{"key":"e_1_2_15_48_1","doi-asserted-by":"publisher","DOI":"10.1002\/path.5230"},{"key":"e_1_2_15_49_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers12071784"},{"key":"e_1_2_15_50_1","doi-asserted-by":"publisher","DOI":"10.1111\/his.13752"},{"key":"e_1_2_15_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2018.09.003"},{"key":"e_1_2_15_52_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.18.01148"},{"key":"e_1_2_15_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2020.02.031"},{"key":"e_1_2_15_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2020.01.003"},{"key":"e_1_2_15_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2019.10.026"},{"key":"e_1_2_15_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.modpat.2024.100557"},{"key":"e_1_2_15_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmoldx.2024.08.005"},{"key":"e_1_2_15_58_1","doi-asserted-by":"publisher","DOI":"10.1002\/path.6062"},{"key":"e_1_2_15_59_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.34715"},{"key":"e_1_2_15_60_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.32737"},{"key":"e_1_2_15_61_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2015.08.034"},{"key":"e_1_2_15_62_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.humpath.2012.01.008"},{"key":"e_1_2_15_63_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.humpath.2010.07.007"},{"key":"e_1_2_15_64_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-018-0312-8"},{"key":"e_1_2_15_65_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/djaa076"},{"key":"e_1_2_15_66_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2019.10.004"},{"key":"e_1_2_15_67_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-58351-6"},{"key":"e_1_2_15_68_1","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0000000000001264"},{"key":"e_1_2_15_69_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ctrv.2020.102000"},{"key":"e_1_2_15_70_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1817323"},{"key":"e_1_2_15_71_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2012.46.5740"},{"key":"e_1_2_15_72_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41585-020-00394-5"},{"key":"e_1_2_15_73_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2035807"},{"key":"e_1_2_15_74_1","doi-asserted-by":"publisher","DOI":"10.37349\/etat.2024.00240"},{"key":"e_1_2_15_75_1","doi-asserted-by":"publisher","DOI":"10.4111\/icu.20200425"},{"key":"e_1_2_15_76_1","doi-asserted-by":"publisher","DOI":"10.3390\/jpm11060473"},{"key":"e_1_2_15_77_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2015.07.009"},{"key":"e_1_2_15_78_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.euo.2020.02.003"},{"key":"e_1_2_15_79_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ctrv.2006.09.006"},{"key":"e_1_2_15_80_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.urolonc.2012.06.014"},{"key":"e_1_2_15_81_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2016.1056"},{"key":"e_1_2_15_82_1","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-14-0623"},{"key":"e_1_2_15_83_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2024.05.014"},{"key":"e_1_2_15_84_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.18521"},{"key":"e_1_2_15_85_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2021.701298"},{"key":"e_1_2_15_86_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2012.01.017"},{"key":"e_1_2_15_87_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2021.802188"},{"key":"e_1_2_15_88_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.euo.2023.05.012"},{"key":"e_1_2_15_89_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.euf.2025.06.009"},{"key":"e_1_2_15_90_1","doi-asserted-by":"publisher","DOI":"10.1080\/14737159.2020.1699791"},{"key":"e_1_2_15_91_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.urolonc.2019.10.013"},{"key":"e_1_2_15_92_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2016.02.056"},{"key":"e_1_2_15_93_1","first-page":"205","article-title":"Prognostic and therapeutic role of HER2 expression in micropapillary carcinoma of the bladder","volume":"10","author":"Sanguedolce F","year":"2019","journal-title":"Mol Clin Oncol"},{"key":"e_1_2_15_94_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.humpath.2018.03.015"},{"key":"e_1_2_15_95_1","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0000000000002416"},{"key":"e_1_2_15_96_1","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-18-0825"},{"key":"e_1_2_15_97_1","doi-asserted-by":"publisher","DOI":"10.1080\/14737140.2025.2543454"}],"container-title":["Histopathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/his.15555","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/his.15555","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/his.15555","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T21:49:49Z","timestamp":1785448189000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/his.15555"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,12]]},"references-count":96,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,1]]}},"alternative-id":["10.1111\/his.15555"],"URL":"https:\/\/doi.org\/10.1111\/his.15555","archive":["Portico"],"relation":{},"ISSN":["0309-0167","1365-2559"],"issn-type":[{"value":"0309-0167","type":"print"},{"value":"1365-2559","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,12]]},"assertion":[{"value":"2025-07-01","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-08-29","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-12-12","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}