{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T04:07:26Z","timestamp":1779250046046,"version":"3.51.4"},"reference-count":20,"publisher":"Springer Science and Business Media LLC","license":[{"start":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T00:00:00Z","timestamp":1779235200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T00:00:00Z","timestamp":1779235200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Universit\u00e4tsklinikum Bonn"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Virchows Arch"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Nectin-4 has been reported to be frequently overexpressed in urothelial carcinoma; however, its expression and diagnostic utility in urothelial carcinoma in situ (CIS) have not been systematically evaluated. In this study, we compared Nectin-4 expression in 50 cases of urothelial CIS and 50 cases of normal or reactive urothelium. Whole sections were immunohistochemically stained for Nectin-4, CK20 and p53, and staining results were evaluated using the H-score. Membranous Nectin-4 expression was significantly higher in urothelial CIS than in normal or reactive urothelium (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.001) (24\/50). A mutation type p53 immunohistochemical pattern was observed in 19\/50 CIS cases (38%), while all benign urothelial samples displayed a wild-type pattern. Aberrant CK20 expression was present in 34\/50 CIS cases (68%). The combination of CK20 and Nectin-4 detected 74% of CIS cases, exceeding the detection rate obtained with the commonly used CK20\/p53 combination (62%) and the Nectin-4\/p53 combination (68%). These findings indicate that Nectin-4 is frequently overexpressed in urothelial CIS and may serve as a useful adjunct immunohistochemical marker, particularly in combination with CK20, for the diagnosis of urothelial CIS.\n                  <\/jats:p>","DOI":"10.1007\/s00428-026-04570-7","type":"journal-article","created":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T03:25:22Z","timestamp":1779247522000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Nectin-4 immunohistochemistry distinguishes urothelial carcinoma in situ from reactive urothelium"],"prefix":"10.1007","author":[{"given":"Anna Katrin","family":"Scherping","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4149-5487","authenticated-orcid":false,"given":"Glen","family":"Kristiansen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2026,5,20]]},"reference":[{"key":"4570_CR1","doi-asserted-by":"publisher","DOI":"10.1200\/po-24-00470","author":"E Crupi","year":"2024","unstructured":"Crupi E, Costa de Padua T, Marandino L et al (2024) Nectin-4 positivity in genitourinary malignancies: a systematic review. JCO Precis Oncol. https:\/\/doi.org\/10.1200\/po-24-00470","journal-title":"JCO Precis Oncol"},{"key":"4570_CR2","doi-asserted-by":"publisher","unstructured":"Chatterjee S, Sinha S, Kundu CN (2021) Nectin cell adhesion molecule-4 (NECTIN-4): a potential target for cancer therapy. Eur J Pharmacol 911. https:\/\/doi.org\/10.1016\/j.ejphar.2021.174516","DOI":"10.1016\/j.ejphar.2021.174516"},{"issue":"10","key":"4570_CR3","doi-asserted-by":"publisher","first-page":"875","DOI":"10.1056\/NEJMoa2312117","volume":"390","author":"T Powles","year":"2024","unstructured":"Powles T, Valderrama BP, Gupta S et al (2024) Enfortumab vedotin and pembrolizumab in untreated advanced urothelial cancer. N Engl J Med 390(10):875\u2013888. https:\/\/doi.org\/10.1056\/NEJMoa2312117","journal-title":"N Engl J Med"},{"issue":"3","key":"4570_CR4","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3390\/cancers17030433","volume":"17","author":"FJ Hsueh","year":"2025","unstructured":"Hsueh FJ, Wang CC, Guo JC, Chueh SC, Tsai YC (2025) Impact of membranous Nectin-4 on outcomes of platinum-based chemotherapy in metastatic urothelial carcinoma. Cancers (Basel) 17(3):1\u201312. https:\/\/doi.org\/10.3390\/cancers17030433","journal-title":"Cancers (Basel)"},{"issue":"8","key":"4570_CR5","doi-asserted-by":"publisher","first-page":"619","DOI":"10.1097\/PAI.0000000000000938","volume":"29","author":"JH Hoffman-Censits","year":"2021","unstructured":"Hoffman-Censits JH, Lombardo KA, Parimi V et al (2021) Expression of Nectin-4 in bladder urothelial carcinoma, in morphologic variants, and nonurothelial histotypes. Appl Immunohistochem Mol Morphol 29(8):619\u2013625. https:\/\/doi.org\/10.1097\/PAI.0000000000000938","journal-title":"Appl Immunohistochem Mol Morphol"},{"issue":"5","key":"4570_CR6","doi-asserted-by":"publisher","first-page":"863","DOI":"10.1111\/his.15130","volume":"84","author":"V Bahlinger","year":"2024","unstructured":"Bahlinger V, Branz A, Strissel PL et al (2024) Associations of TACSTD2\/TROP2 and NECTIN-4\/NECTIN-4 with molecular subtypes, PD-L1 expression, and FGFR3 mutational status in two advanced urothelial bladder cancer cohorts. Histopathology 84(5):863\u2013876. https:\/\/doi.org\/10.1111\/his.15130","journal-title":"Histopathology"},{"key":"4570_CR7","doi-asserted-by":"publisher","DOI":"10.3390\/diagnostics15172163","author":"F Sanguedolce","year":"2025","unstructured":"Sanguedolce F, Cormio A, Zanelli M et al (2025) Diagnostic, prognostic, and predictive tissue biomarkers in urothelial carcinoma in situ: a narrative review. 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Formal written informed consent was not required.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics statement"}},{"value":"The authors declare no conflict of interest.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflicts of interest"}}]}}