{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T13:35:21Z","timestamp":1792157721536,"version":"4.4.0"},"reference-count":29,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2024,1,9]],"date-time":"2024-01-09T00:00:00Z","timestamp":1704758400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100005564","name":"Gilead Sciences","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005564","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["493665037"],"award-info":[{"award-number":["493665037"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Histopathology"],"published-print":{"date-parts":[[2024,4]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>Treatment options for advanced urothelial carcinoma (aUC) rapidly evolved: besides immunomodulative therapeutic options and inhibitors targeting <jats:italic>Fibroblast growth factor receptor (FGFR)<\/jats:italic> alterations, two new antibody\u2010drug conjugates (ADC), sacituzumab govitecan (SG) and enfortumab vedotin (EV), have been approved. However, little is known about the associations of specific aUC properties and the surface target expression of TROP2 and NECTIN\u20104. Our aim was to characterize associations of <jats:italic>TACSTD2<\/jats:italic>\/TROP2 and <jats:italic>NECTIN\u20104<\/jats:italic>\/NECTIN\u20104 protein and gene expression with morphomolecular and clinicopathological characteristics of aUC in two large independent cohorts.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and results<\/jats:title><jats:p>The TCGA BLCA (<jats:italic>n<\/jats:italic>\u2009=\u2009405) and the CCC\u2010EMN (<jats:italic>n<\/jats:italic>\u2009=\u2009247) cohorts were retrospectively analysed. TROP2\/<jats:italic>TACSTD2<\/jats:italic> and NECTIN\u20104\/<jats:italic>NECTIN\u20104<\/jats:italic> are highly expressed at the protein and transcript level in aUC, and their expression status did not correlate with patient survival in both cohorts. NECTIN\u20104\/<jats:italic>NECTIN\u20104<\/jats:italic> expression was higher in luminal tumours and reduced in squamous aUCs. NECTIN\u20104 was negative in 10.6% of samples, and 18.4% of samples had low expression (<jats:italic>H<\/jats:italic>\u2010score &lt;15). The TROP2 negativity rate amounted to 6.5%. <jats:italic>TACSTD2<\/jats:italic> and <jats:italic>NECTIN\u20104<\/jats:italic> expression was reduced in neuroendocrine\u2010like and\/or protein\u2010based double\u2010negative tumours. TROP2\u2010 and NECTIN\u20104\u2010negative tumours included one sarcomatoid and four neuroendocrine aUC. <jats:italic>FGFR3<\/jats:italic> alterations and PD\u2010L1 expression on tumour and immune cells did not associate with TROP2 or NECTIN\u20104 expression.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p><jats:italic>TACSTD2<\/jats:italic>\/TROP2 and <jats:italic>NECTIN\u20104<\/jats:italic>\/NECTIN\u20104 are widely expressed in aUC, independent of <jats:italic>FGFR3<\/jats:italic> alterations or PD\u2010L1 expression, thus representing a suitable target for ADC treatment in the majority of aUC. The expression loss was associated with aggressive morphomolecular aUC subtypes, i.e. neuroendocrine(\u2010like) and sarcomatoid aUC.<\/jats:p><\/jats:sec>","DOI":"10.1111\/his.15130","type":"journal-article","created":{"date-parts":[[2024,1,10]],"date-time":"2024-01-10T06:40:30Z","timestamp":1704868830000},"page":"863-876","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":54,"title":["Associations of <i>TACSTD2<\/i>\/<scp>TROP2<\/scp> and <i>NECTIN\u20104<\/i>\/<scp>NECTIN<\/scp>\u20104 with molecular subtypes, <scp>PD\u2010L1<\/scp> expression, and <i>FGFR3<\/i> mutational status in two advanced urothelial bladder cancer cohorts"],"prefix":"10.1111","volume":"84","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5919-7651","authenticated-orcid":false,"given":"Veronika","family":"Bahlinger","sequence":"first","affiliation":[{"name":"Institute of Pathology, University Hospital Erlangen, Friedrich\u2010Alexander Universit\u00e4t Erlangen\u2010N\u00fcrnberg  Erlangen Germany"},{"name":"Comprehensive Cancer Center EMN University Hospital Erlangen, Friedrich\u2010Alexander\u2010Universit\u00e4t Erlangen\u2010N\u00fcrnberg  Erlangen Germany"},{"name":"Bayerisches Zentrum f\u00fcr Krebsforschung (BZKF) Site University Hospital Erlangen  Erlangen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annalena","family":"Branz","sequence":"additional","affiliation":[{"name":"Institute of Pathology, University Hospital Erlangen, Friedrich\u2010Alexander Universit\u00e4t Erlangen\u2010N\u00fcrnberg  Erlangen Germany"},{"name":"Comprehensive Cancer Center EMN University Hospital Erlangen, Friedrich\u2010Alexander\u2010Universit\u00e4t Erlangen\u2010N\u00fcrnberg  Erlangen Germany"},{"name":"Bayerisches Zentrum f\u00fcr Krebsforschung (BZKF) Site University Hospital Erlangen  Erlangen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pamela L","family":"Strissel","sequence":"additional","affiliation":[{"name":"Institute of Pathology, University Hospital Erlangen, Friedrich\u2010Alexander Universit\u00e4t Erlangen\u2010N\u00fcrnberg  Erlangen Germany"},{"name":"Comprehensive Cancer Center EMN University Hospital Erlangen, Friedrich\u2010Alexander\u2010Universit\u00e4t Erlangen\u2010N\u00fcrnberg  Erlangen Germany"},{"name":"Bayerisches Zentrum f\u00fcr Krebsforschung (BZKF) Site University Hospital Erlangen  Erlangen Germany"},{"name":"Laboratory for Molecular Medicine, Department of Gynecology and Obstetrics University Hospital Erlangen, Friedrich\u2010Alexander University Erlangen\u2010N\u00fcrnberg  Erlangen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reiner","family":"Strick","sequence":"additional","affiliation":[{"name":"Comprehensive Cancer Center EMN University Hospital Erlangen, Friedrich\u2010Alexander\u2010Universit\u00e4t Erlangen\u2010N\u00fcrnberg  Erlangen 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