{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T13:35:23Z","timestamp":1792157723437,"version":"4.4.0"},"reference-count":28,"publisher":"Springer Science and Business Media LLC","issue":"3","license":[{"start":{"date-parts":[[2025,9,11]],"date-time":"2025-09-11T00:00:00Z","timestamp":1757548800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2025,9,11]],"date-time":"2025-09-11T00:00:00Z","timestamp":1757548800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Virchows Arch"],"published-print":{"date-parts":[[2026,3]]},"DOI":"10.1007\/s00428-025-04243-x","type":"journal-article","created":{"date-parts":[[2025,9,11]],"date-time":"2025-09-11T21:54:14Z","timestamp":1757627654000},"page":"499-510","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Immunohistochemical expression of Nectin-4 and potential implications for enfortumab vedotin therapy in germ cell tumors of the testis: a preliminary study"],"prefix":"10.1007","volume":"488","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7254-4195","authenticated-orcid":false,"given":"Costantino","family":"Ricci","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9046-1115","authenticated-orcid":false,"given":"Francesca","family":"Ambrosi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2897-7756","authenticated-orcid":false,"given":"Tania","family":"Franceschini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessia","family":"Grillini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eugenia","family":"Franchini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1145-6025","authenticated-orcid":false,"given":"Francesco","family":"Vasuri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-8560-1925","authenticated-orcid":false,"given":"Agnese","family":"Orsatti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1809-3826","authenticated-orcid":false,"given":"Luisa","family":"Di Sciascio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6476-6871","authenticated-orcid":false,"given":"Francesco","family":"Massari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5169-3631","authenticated-orcid":false,"given":"Veronica","family":"Mollica","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7892-9619","authenticated-orcid":false,"given":"Andrea","family":"Marchetti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3331-0374","authenticated-orcid":false,"given":"Federico Mineo","family":"Bianchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1914-0743","authenticated-orcid":false,"given":"Maurizio","family":"Colecchia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0164-5911","authenticated-orcid":false,"given":"Andres Martin","family":"Acosta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6829-1391","authenticated-orcid":false,"given":"Jo\u00e3o","family":"Lobo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1749-150X","authenticated-orcid":false,"given":"Michelangelo","family":"Fiorentino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,9,11]]},"reference":[{"key":"4243_CR1","unstructured":"WHO Classifications of Tumors Editorial Board (2022) Urinary and male genital tumours 5th edn. International Agency for Research on Cancer, Lyon, France."},{"issue":"4","key":"4243_CR2","doi-asserted-by":"publisher","first-page":"513","DOI":"10.1111\/his.13115","volume":"70","author":"MT Idrees","year":"2017","unstructured":"Idrees MT, Ulbright TM, Oliva E et al (2017) The World Health Organization 2016 classification of testicular non-germ cell tumours: a review and update from the International Society of Urological Pathology Testis Consultation Panel. Histopathology 70(4):513\u2013521","journal-title":"Histopathology"},{"key":"4243_CR3","doi-asserted-by":"crossref","unstructured":"Berney DM, Cree I, Rao V et al (20220) An introduction to the WHO 5th edition 2022 classification of testicular tumours. Histopathology 81(4):459\u201366.","DOI":"10.1111\/his.14675"},{"key":"4243_CR4","doi-asserted-by":"publisher","first-page":"7182014","DOI":"10.1155\/2018\/7182014","volume":"2018","author":"M Nayan","year":"2018","unstructured":"Nayan M, Hamilton RJ (2018) Dissecting the evolving risk of relapse over time in surveillance for testicular cancer. Adv Urol 2018:7182014","journal-title":"Adv Urol"},{"issue":"1","key":"4243_CR5","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1097\/PAS.0b013e3182a2926e","volume":"38","author":"I Alvarado-Cabrero","year":"2014","unstructured":"Alvarado-Cabrero I, Hern\u00e1ndez-Toriz N, Paner GP (2014) Clinicopathologic analysis of choriocarcinoma as a pure or predominant component of germ cell tumor of the testis. Am J Surg Pathol 38(1):111\u2013118","journal-title":"Am J Surg Pathol"},{"key":"4243_CR6","unstructured":"Moul JW, McCarthy WF, Fernandez EB et al (1994) Percentage of embryonal carcinoma and of vascular invasion predicts pathological stage in clinical stage I nonseminomatous testicular cancer. Cancer Res 15;54(2):362\u20134."},{"issue":"10","key":"4243_CR7","doi-asserted-by":"publisher","first-page":"e033713","DOI":"10.1136\/bmjopen-2019-033713","volume":"9","author":"T Wagner","year":"2019","unstructured":"Wagner T, Toft BG, Engvad B et al (2019) Prognostic factors for relapse in patients with clinical stage I testicular cancer: protocol for a Danish nationwide cohort study. BMJ Open 9(10):e033713","journal-title":"BMJ Open"},{"issue":"5","key":"4243_CR8","doi-asserted-by":"publisher","first-page":"743","DOI":"10.1111\/his.15288","volume":"85","author":"AM Acosta","year":"2024","unstructured":"Acosta AM, Berney DM, Lobo J et al (2024) Proposal for a reappraisal of the current classification of so-called \u201csomatic-type\u201d malignancies arising in germ cell tumours. Histopathology 85(5):743\u2013745","journal-title":"Histopathology"},{"issue":"4","key":"4243_CR9","first-page":"389","volume":"18","author":"C Oing","year":"2018","unstructured":"Oing C, Seidel C, Bokemeyer C (2018) Therapeutic approaches for refractory germ cell cancer 18(4):389\u2013397","journal-title":"Therapeutic approaches for refractory germ cell cancer"},{"issue":"1","key":"4243_CR10","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1093\/annonc\/mdx680","volume":"29","author":"N Adra","year":"2018","unstructured":"Adra N, Einhorn LH, Althouse SK et al (2018) Phase II trial of pembrolizumab in patients with platinum refractory germ-cell tumors: a Hoosier Cancer Research Network study GU14-206. Ann Oncol 29(1):209\u2013214","journal-title":"Ann Oncol"},{"issue":"5","key":"4243_CR11","doi-asserted-by":"publisher","first-page":"303.e1","DOI":"10.1016\/j.urolonc.2021.02.014","volume":"39","author":"M Al-Hogbani","year":"2021","unstructured":"Al-Hogbani M, Duguay J, Wagner DC et al (2021) Expression of programmed death ligand-1 (PD-L1) in metastatic and postchemotherapy viable testicular germ cell tumors. Urol Oncol 39(5):303.e1-e8","journal-title":"Urol Oncol"},{"key":"4243_CR12","doi-asserted-by":"publisher","first-page":"154540","DOI":"10.1016\/j.prp.2023.154540","volume":"247","author":"S Melotti","year":"2023","unstructured":"Melotti S, Ambrosi F, Franceschini T et al (2023) TAMs PD-L1(+) in the reprogramming of germ cell tumors of the testis. Pathol Res Pract 247:154540","journal-title":"Pathol Res Pract"},{"issue":"12","key":"4243_CR13","doi-asserted-by":"publisher","first-page":"1125","DOI":"10.1056\/NEJMoa2035807","volume":"384","author":"T Powles","year":"2021","unstructured":"Powles T, Rosenberg JE, Sonpavde GP et al (2021) Enfortumab vedotin in previously treated advanced urothelial carcinoma. N Engl J Med 384(12):1125\u20131135","journal-title":"N Engl J Med"},{"issue":"22","key":"4243_CR14","doi-asserted-by":"publisher","first-page":"2474","DOI":"10.1200\/JCO.20.03489","volume":"39","author":"ST Tagawa","year":"2021","unstructured":"Tagawa ST, Balar AV, Petrylak DP et al (2021) TROPHY-U-01: a phase II open-label study of sacituzumab govitecan in patients with metastatic urothelial carcinoma progressing after platinum-based chemotherapy and checkpoint inhibitors. J Clin Oncol 39(22):2474\u20132485","journal-title":"J Clin Oncol"},{"issue":"10","key":"4243_CR15","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","journal-title":"N Engl J Med"},{"key":"4243_CR16","doi-asserted-by":"publisher","first-page":"174516","DOI":"10.1016\/j.ejphar.2021.174516","volume":"911","author":"S Chatterjee","year":"2021","unstructured":"Chatterjee S, Sinha S, Kundu CN et al (2021) Nectin cell adhesion molecule-4 (NECTIN-4): a potential target for cancer therapy. Eur J Pharmacol 911:174516","journal-title":"Eur J Pharmacol"},{"issue":"1","key":"4243_CR17","doi-asserted-by":"publisher","first-page":"166","DOI":"10.1186\/s12881-018-0681-y","volume":"19","author":"M Ito","year":"2018","unstructured":"Ito M, Nishizawa H, Tsutsumi M et al (2018) Potential role for nectin-4 in the pathogenesis of pre-eclampsia: a molecular genetic study. BMC Med Genet 19(1):166","journal-title":"BMC Med Genet"},{"issue":"3","key":"4243_CR18","first-page":"200","volume":"9","author":"H Yoshizawa","year":"2023","unstructured":"Yoshizawa H, Nishizawa H, Ito M et al (2023) Increased levels of nectin-4 as a serological marker for pre-eclampsia. Fujita Med J 9(3):200\u2013205","journal-title":"Fujita Med J"},{"issue":"20","key":"4243_CR19","doi-asserted-by":"publisher","first-page":"2446","DOI":"10.1200\/JCO.23.01983","volume":"42","author":"N Kl\u00fcmper","year":"2024","unstructured":"Kl\u00fcmper N, Tran NK, Zsch\u00e4bitz S et al (2024) Nectin4 amplification is frequent in solid tumors and predicts enfortumab vedotin response in metastatic urothelial cancer. J Clin Oncol 42(20):2446\u20132455","journal-title":"J Clin Oncol"},{"issue":"8","key":"4243_CR20","doi-asserted-by":"publisher","first-page":"1496","DOI":"10.1158\/1078-0432.CCR-22-1764","volume":"29","author":"N Kl\u00fcmper","year":"2023","unstructured":"Kl\u00fcmper N, Ralser DJ, Ellinger J et al (2023) Membranous NECTIN-4 expression frequently decreases during metastatic spread of urothelial carcinoma and is associated with enfortumab vedotin resistance. Clin Cancer Res 29(8):1496\u20131505","journal-title":"Clin Cancer Res"},{"issue":"10","key":"4243_CR21","doi-asserted-by":"publisher","first-page":"3003","DOI":"10.1158\/0008-5472.CAN-15-1313","volume":"76","author":"PM Challita-Eid","year":"2016","unstructured":"Challita-Eid PM, Satpayev D, Yang P et al (2016) Enfortumab vedotin antibody-drug conjugate targeting Nectin-4 is a highly potent therapeutic agent in multiple preclinical cancer models. Cancer Res 76(10):3003\u20133013","journal-title":"Cancer Res"},{"key":"4243_CR22","doi-asserted-by":"publisher","DOI":"10.1016\/j.modpat.2025.100781","author":"JN Mink","year":"2025","unstructured":"Mink JN, Eckstein M, Khalmurzaev O et al (2025) Evaluation of Nectin-4 and Trop-2: implications for patient outcomes and therapy in penile cancer. Mod Pathol. https:\/\/doi.org\/10.1016\/j.modpat.2025.100781","journal-title":"Mod Pathol"},{"issue":"3","key":"4243_CR23","doi-asserted-by":"publisher","first-page":"465","DOI":"10.1111\/his.14968","volume":"83","author":"C Ricci","year":"2023","unstructured":"Ricci C, Ambrosi F, Franceschini T et al (2023) FoxA2 is a reliable marker for the diagnosis of yolk sac tumour postpubertal-type. Histopathology 83(3):465\u2013476","journal-title":"Histopathology"},{"key":"4243_CR24","doi-asserted-by":"publisher","first-page":"154044","DOI":"10.1016\/j.prp.2022.154044","volume":"237","author":"A Orsatti","year":"2022","unstructured":"Orsatti A, Sirolli M, Ambrosi F et al (2022) SOX2 and PRAME in the \u201creprogramming\u201d of seminoma cells. Pathol Res Pract 237:154044","journal-title":"Pathol Res Pract"},{"issue":"5","key":"4243_CR25","doi-asserted-by":"publisher","first-page":"644","DOI":"10.1093\/ajcp\/aqab200","volume":"157","author":"C Ricci","year":"2022","unstructured":"Ricci C, Franceschini T, Giunchi F et al (2022) Immunohistochemical expression of preferentially expressed antigen in melanoma (PRAME) in the uninvolved background testis, germ cell neoplasia in situ, and germ cell tumors of the testis. Am J Clin Pathol 157(5):644\u2013648","journal-title":"Am J Clin Pathol"},{"key":"4243_CR26","doi-asserted-by":"publisher","unstructured":"Zhang J, Liu R, Wang S et al (2025) 9MW2821, a next-generation Nectin-4 targeting antibody-drug conjugate, in patients with advanced solid tumors: a first-in-human, open label, multicenter, phase I\/II study. Ann Oncol Apr 25:S0923\u20137534(25)00169\u20133. https:\/\/doi.org\/10.1016\/j.annonc.2025.04.009. Online ahead of print.","DOI":"10.1016\/j.annonc.2025.04.009"},{"issue":"3","key":"4243_CR27","doi-asserted-by":"publisher","first-page":"473","DOI":"10.2967\/jnumed.124.269024","volume":"66","author":"L Sun","year":"2025","unstructured":"Sun L, Sun Y, Zuo K et al (2025) Pilot study of Nectin-4-targeted PET imaging agent 68Ga-FZ-NR-1 in triple-negative breast cancer from bench to first-in-human. J Nucl Med 66(3):473\u2013479","journal-title":"J Nucl Med"},{"issue":"4","key":"4243_CR28","doi-asserted-by":"publisher","first-page":"493","DOI":"10.1158\/1535-7163.MCT-21-0846","volume":"21","author":"W Bouleftour","year":"2022","unstructured":"Bouleftour W, Guillot A, Magne N (2022) The anti-Nectin 4: a promising tumor cells target. A systematic review. Mol Cancer Ther 21(4):493\u2013501","journal-title":"Mol Cancer Ther"}],"container-title":["Virchows Archiv"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00428-025-04243-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00428-025-04243-x","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00428-025-04243-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,5]],"date-time":"2026-03-05T07:10:41Z","timestamp":1772694641000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00428-025-04243-x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,11]]},"references-count":28,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2026,3]]}},"alternative-id":["4243"],"URL":"https:\/\/doi.org\/10.1007\/s00428-025-04243-x","relation":{},"ISSN":["0945-6317","1432-2307"],"issn-type":[{"value":"0945-6317","type":"print"},{"value":"1432-2307","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,11]]},"assertion":[{"value":"19 June 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 July 2025","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 August 2025","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 September 2025","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"All clinicopathologic investigations were conducted according to the principles of the Declaration of Helsinki and all information regarding the human material used in this study has been managed using anonymous numerical codes. The study was approved by the local ethics committee\/CE-AVEC Bologna-Emilia Romagna (68\/2025\/Tess\/AOUBo). All patients included in the study provided informed consent, after a consultation with the investigators.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Compliance with ethical standards"}},{"value":"The study was approved by the local ethics committee\/CE-AVEC Bologna-Emilia Romagna (68\/2025\/Tess\/AOUBo).","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Study-specific approval by the appropriate ethics committee for research involving humans and\/or animals"}},{"value":"All patients included in the study provided informed consent after a consultation with the investigators.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Informed consent if the research involved human participants"}},{"value":"The authors declare no competing interests.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}