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Importantly, nectin\u20104 expression in bladder cancer is associated with response to enfortumab vedotin, and PD\u2010L1 expression is associated with responses to immune checkpoint inhibitors (ICIs).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The authors conducted a retrospective review identifying 117 patients with advanced or metastatic BCDD who were treated at Winship Cancer Institute from 2011 to 2021. They performed immunohistochemistry staining for nectin\u20104 and PD\u2010L1 expression by histologic subtype as well as genomic analysis of these patients, including RNA sequencing, whole\u2010exome sequencing, and fusion detection analysis as well as a subgroup genomic analysis of patients with BCDD who received ICIs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The results indicated that nectin\u20104 expression was highest in the groups who had the squamous and plasmacytoid subtypes, whereas the group that had the sarcomatoid subtype (70.8%) had the highest proportion of PD\u2010L1\u2013positive patients. Genomic analysis yielded several key findings, including a 50% RB1 mutation rate in patients who had small cell BCDD, targetable PIK3CA mutations across multiple subtypes of BCDD, and significantly higher expression of TEC in responders to ICIs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>In this study, the authors identified clinically relevant data on nectin\u20104 and PD\u2010L1 expression in patients with rare bladder tumors. They also identified several novel findings in the genomic analysis that highlight the role of precision medicine in this population of patients. Larger, prospective studies are needed to validate these hypothesis\u2010generating data.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cncr.35465","type":"journal-article","created":{"date-parts":[[2024,7,3]],"date-time":"2024-07-03T13:45:01Z","timestamp":1720014301000},"page":"3658-3670","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["PD\u2010L1 and nectin\u20104 expression and genomic characterization of bladder cancer with divergent differentiation"],"prefix":"10.1002","volume":"130","author":[{"given":"Dylan J.","family":"Martini","sequence":"first","affiliation":[{"name":"Department of Medicine Massachusetts General Hospital  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine B.","family":"Case","sequence":"additional","affiliation":[{"name":"Emory University School of Medicine  Atlanta Georgia 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