{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,5]],"date-time":"2026-03-05T08:30:39Z","timestamp":1772699439873,"version":"3.50.1"},"reference-count":29,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2018,6,19]],"date-time":"2018-06-19T00:00:00Z","timestamp":1529366400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004359","name":"Vetenskapsr\u00e5det","doi-asserted-by":"publisher","award":["2015\u201002767"],"award-info":[{"award-number":["2015\u201002767"]}],"id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002794","name":"Cancerfonden","doi-asserted-by":"publisher","award":["2016\/314"],"award-info":[{"award-number":["2016\/314"]}],"id":[{"id":"10.13039\/501100002794","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002794","name":"Cancerfonden","doi-asserted-by":"publisher","award":["2014\/448"],"award-info":[{"award-number":["2014\/448"]}],"id":[{"id":"10.13039\/501100002794","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003461","name":"Gunnar Nilssons Cancerstiftelse","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003461","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["febs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molecular Oncology"],"published-print":{"date-parts":[[2018,8]]},"abstract":"<jats:p>Lynch syndrome confers an increased risk for urothelial carcinoma (<jats:styled-content style=\"fixed-case\">UC<\/jats:styled-content>). Molecular subtypes may be relevant to prognosis and therapeutic possibilities, but have to date not been defined in Lynch syndrome\u2010associated urothelial cancer. We aimed to provide a molecular description of Lynch syndrome\u2010associated <jats:styled-content style=\"fixed-case\">UC<\/jats:styled-content>. Thus, Lynch syndrome\u2010associated <jats:styled-content style=\"fixed-case\">UC<\/jats:styled-content>s of the upper urinary tract and the urinary bladder were identified in the Danish hereditary nonpolyposis colorectal cancer (<jats:styled-content style=\"fixed-case\">HNPCC<\/jats:styled-content>) register and were transcriptionally and immunohistochemically profiled and further related to data from 307 sporadic urothelial carcinomas. Whole\u2010genome <jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content> expression profiles of 41 tumors and immunohistochemical stainings against <jats:styled-content style=\"fixed-case\">FGFR<\/jats:styled-content>3, <jats:styled-content style=\"fixed-case\">KRT<\/jats:styled-content>5, <jats:styled-content style=\"fixed-case\">CCNB<\/jats:styled-content>1, <jats:styled-content style=\"fixed-case\">RB<\/jats:styled-content>1, and <jats:styled-content style=\"fixed-case\">CDKN<\/jats:styled-content>2A (p16) of 37 tumors from patients with Lynch syndrome were generated. Pathological data, microsatellite instability, anatomic location, and overall survival data were analyzed and compared with sporadic bladder cancer. The 41 Lynch syndrome\u2010associated <jats:styled-content style=\"fixed-case\">UC<\/jats:styled-content> developed at a mean age of 61\u00a0years with 59% women. <jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content> expression profiling and immunostaining classified the majority of the Lynch syndrome\u2010associated <jats:styled-content style=\"fixed-case\">UC<\/jats:styled-content> as urothelial\u2010like tumors with only 20% being genomically unstable, basal\/SCC\u2010like, or other subtypes. The subtypes were associated with stage, grade, and microsatellite instability. Comparison to larger datasets revealed that Lynch syndrome\u2010associated <jats:styled-content style=\"fixed-case\">UC<\/jats:styled-content> shares molecular similarities with sporadic <jats:styled-content style=\"fixed-case\">UC<\/jats:styled-content>. In conclusion, transcriptomic and immunohistochemical profiling identifies a predominance of the urothelial\u2010like molecular subtype in Lynch syndrome and reveals that the molecular subtypes of sporadic bladder cancer are relevant also within this hereditary, mismatch\u2010repair defective subset.<\/jats:p>","DOI":"10.1002\/1878-0261.12325","type":"journal-article","created":{"date-parts":[[2018,5,23]],"date-time":"2018-05-23T14:53:05Z","timestamp":1527087185000},"page":"1286-1295","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Molecular subtype classification of urothelial carcinoma in Lynch syndrome"],"prefix":"10.1002","volume":"12","author":[{"given":"Christina","family":"Therkildsen","sequence":"first","affiliation":[{"name":"The HNPCC register Clinical Research Center Copenhagen University Hospital Hvidovre 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