{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T17:58:55Z","timestamp":1791309535594,"version":"4.3.1"},"reference-count":22,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,1,13]],"date-time":"2025-01-13T00:00:00Z","timestamp":1736726400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["bjui-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["BJU International"],"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To investigate the expression patterns of Nectin\u20104, the target molecule of the antibody\u2010drug conjugate enfortumab vedotin (EV), in relation to histological and molecular subtypes of urothelial bladder cancer (UBC).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Patients and Methods<\/jats:title>\n                    <jats:p>We assessed the protein expression patterns of Nectin\u20104 in a spatially organised tissue microarray containing 1386 tissue cores from 314 consecutive patients with UBC who underwent radical cystectomy (2005\u20132018). Results were correlated with clinicopathological and follow\u2010up data, as well as with different spatial locations (tumour central vs tumour\u2010normal interface and primary tumour vs lymph node [LN] metastases). Additionally, we correlated Nectin\u20104 expression levels with histological and molecular subtypes. Finally, we assessed the value of Nectin\u20104 expression for predicting the efficacy of platinum therapy in the peri\u2010operative setting.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Nectin\u20104 expression was observed in 63% of primary tumours and 87% of LN metastases, with significantly higher levels in LNs. Of the histological subtypes, the micropapillary (58%) and pure urothelial histologies (30%) were associated with the highest Nectin\u20104 positivity, while the sarcomatoid (17%), squamous (15%) and small\/cell\u2010neuroendocrine (0%) subtypes exhibited the lowest. Nectin\u20104 immunopositivity rates were significantly higher in luminal (urothelial\u2010like [42%] and genomically unstable [34%] Lund subtypes) compared to the basal (5%) or mesenchymal (0%) molecular subtypes. Higher Nectin\u20104 expression levels were associated with lower tumour stage but showed no association with overall survival. Finally, patients with low Nectin\u20104 expression tended to derive more benefit from platinum\u2010based chemotherapy in both adjuvant and neoadjuvant settings (\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&lt;\u20090.001,\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.067).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our results revealed a low spatial heterogeneity of Nectin\u20104 expression within the primary tumour. In contrast, differential Nectin\u20104 expression was found in the context of histological and molecular subtypes. Nectin\u20104\u2010expressing tumours may show varying sensitivity to both EV and platinum\u2010based chemotherapy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/bju.16643","type":"journal-article","created":{"date-parts":[[2025,1,13]],"date-time":"2025-01-13T03:33:47Z","timestamp":1736739227000},"page":"297-305","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Spatial distribution and subtype\u2010specific expression patterns of Nectin\u20104 in muscle\u2010invasive bladder cancer"],"prefix":"10.1111","volume":"136","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4775-2432","authenticated-orcid":false,"given":"Csilla","family":"Olah","sequence":"first","affiliation":[{"name":"Department of Urology University of Duisburg\u2010Essen  Essen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lara","family":"Sichward","sequence":"additional","affiliation":[{"name":"Institute of Pathology, University Medicine Essen University of Duisburg\u2010Essen  Essen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Boris","family":"Hadaschik","sequence":"additional","affiliation":[{"name":"Department of Urology University of Duisburg\u2010Essen  Essen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Darr","sequence":"additional","affiliation":[{"name":"Department of Urology University of Duisburg\u2010Essen  Essen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Viktor","family":"Gr\u00fcnwald","sequence":"additional","affiliation":[{"name":"Department of Urology University of Duisburg\u2010Essen  Essen Germany"},{"name":"Department of Medical Oncology University of Duisburg\u2010Essen  Essen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulrich","family":"Krafft","sequence":"additional","affiliation":[{"name":"Department of Urology University of Duisburg\u2010Essen  Essen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara T.","family":"Gr\u00fcnwald","sequence":"additional","affiliation":[{"name":"Department of Urology University of Duisburg\u2010Essen  Essen Germany"},{"name":"Princess Margaret Cancer Centre  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Osama","family":"Mahmoud","sequence":"additional","affiliation":[{"name":"Department of Urology University of Duisburg\u2010Essen  Essen Germany"},{"name":"Department of Urology, Qena Faculty of Medicine South Valley University  Qena Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mulham","family":"Al\u2010Nader","sequence":"additional","affiliation":[{"name":"Department of Urology University of Duisburg\u2010Essen  Essen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Nyirady","sequence":"additional","affiliation":[{"name":"Department of 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