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New strategies such as immune checkpoint inhibitors (ICI) or antibody-drug conjugates (ADC) are lacking. One potential target for the ADC Enfortumab Vedotin (EV) is Nectin-4. EV has been successfully used to treat metastatic urothelial carcinoma (mUC). Currently, there is limited data on the expression of Nectin-4 for VSCC. Our aim was therefore to investigate the expression of Nectin-4 in women with VSCC. In total, 219 formalin-fixed paraffin-embedded tissue (FFPE) samples of primary VSCC were collected between 2000 and 2021. A next generation tissue microarray (ngTMA) was constructed. The assessment of Nectin-4 expression was performed through the implementation of immunohistochemistry (IHC). We also performed NECTIN-4 fluorescence in situ hybridization (FISH) to evaluate amplification of Nectin-4. The median Nectin-4 H-score for membranous expression was 22.5, with 32.4% of VSCCs exhibiting moderate to strong expression. We could not show that Nectin-4 H-score (membranous) significantly influenced overall survival in addition to other prognostic factors. The rates of regional lymph node metastases, lymphatic vascular space involvement, G3-Grading, perineural sheath invasion and p16-\/p53+\u2009were highest in Nectin-4-negative VSCC. 28.8% of recurrent VSCC had moderate or strong expression of Nectin-4. None of the investigated VSCC (primary or recurrent) showed amplification of Nectin-4 in contrast to mUC. Nectin-4 could be a potential target in the therapy of women with VSCC. Further (pre-)clinical data is needed to evaluate the use of EV in therapy of women with VSCC.<\/jats:p>","DOI":"10.1007\/s00428-026-04495-1","type":"journal-article","created":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T17:01:05Z","timestamp":1774544465000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Nectin-4 expression in vulvar squamous cell carcinoma"],"prefix":"10.1007","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0729-2064","authenticated-orcid":false,"given":"Frederik A.","family":"Stuebs","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antje","family":"Kn\u00f6ll","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arndt","family":"Hartmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Matek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nelson","family":"John","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lothar","family":"H\u00e4berle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias W.","family":"Beckmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos","family":"Bercebal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"Eckstein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastian","family":"Rauch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carol I.","family":"Geppert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,3,26]]},"reference":[{"key":"4495_CR1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22010190","author":"F Borella","year":"2020","unstructured":"Borella F et al (2020) Is there a place for immune checkpoint inhibitors in vulvar neoplasms? 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