Choriocarcinoma (CHC) is an aggressive tumor that expresses Nectin-4, which makes it a potential target for enfortumab vedotin (EV). However, only a few cases have been analyzed so far, and the correlation between Nectin-4 and clinical-pathological features has never been investigated.
Twenty-one testicular CHCs were collected and stained for Nectin-4. Cytoplasmatic expression was positive in 17/20 primary CHCs (4/20: moderate expression). Membrane expression was positive in 16/20 primary CHCs (5/20: moderate expression). Cytoplasmatic expression was associated with higher % of CHC (p = 0.028) and β-HCG serum levels (p = 0.007); moderate/strong cytoplasmatic expression was associated with younger age (p = 0.0039). The only post-chemotherapy and metastatic CHC showed the highest membrane expression (H-score: 155), especially if paired with its primary (H-score: 33). The Nectin-4 stain was primarily confined to syncytiotrophoblasts rather than to cytotrophoblasts/intermediate trophoblasts. These findings confirm that testicular CHC expresses Nectin-4 and may be potentially targetable with EV. Future studies are needed to verify whether metastasis and chemotherapy up-regulate Nectin-4 and increase the sensitivity to EV, and whether the absence of Nectin-4 expression by cytotrophoblasts (the proliferative population of CHC) influences its potential efficacy.
Virchows Archiv : an international journal of pathology. 2026 Jan 21 [Epub ahead of print]
Costantino Ricci, Luisa Di Sciascio, Francesca Ambrosi, Agnese Orsatti, Alessia Grillini, Eugenia Franchini, Veronica Mollica, Francesco Massari, Federico Mineo Bianchi, Francesco Vasuri, João Lobo, Nuno Tiago Tavares, Fernanda Fernandes-Pontes, Andres Martin Acosta, Michelangelo Fiorentino
Pathology Unit, DIAP-Dipartimento Interaziendale Di Anatomia Patologica Di Bologna, Maggiore Hospital-AUSL Bologna, Via Dell'Ospedale 8, 40133, Bologna, Italy. ., Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna, Italy., Pathology Unit, DIAP-Dipartimento Interaziendale Di Anatomia Patologica Di Bologna, Maggiore Hospital-AUSL Bologna, Via Dell'Ospedale 8, 40133, Bologna, Italy., Medical Oncology, IRCCS Azienda Ospedaliero, Universitaria Di Bologna, Bologna, Italy., Urology Department, Maggiore Hospital-AUSL Bologna, Bologna, Italy., Department of Pathology, Portuguese Oncology Institute of Porto (IPOP), Porto, Portugal., Cancer Biology and Epigenetics Group, Research Center of IPO Porto (GEBC CI-IPOP)/RISE@CI-IPOP (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto)/Porto Comprehensive Cancer Center (P.CCC), Porto, Portugal., Department of Pathology, Indiana University School of Medicine, Indianapolis, USA.
PubMed http://www.ncbi.nlm.nih.gov/pubmed/41559359