A subset of germ cell tumors of the testis (GCTT) shows an aggressive clinical behavior, with chemo-resistance, metastases, and recurrences. Recently, enfortumab vedotin (EV), an antibody-drug conjugate (ADC) targeting Nectin-4, has been shown to improve the survival in urothelial carcinoma and has been approved for the locally advanced or metastatic cases.
We stained for Nectin-4 (EPR15613-68 rb, Abcam) 46 cases (42 chemo-naive primary testicular tumors and 4 post-chemotherapy metastatic recurrences) and adopted the H-score and the specific Nectin-4 score (negative (H-score 0-14), weak (H-score 15-99), moderate (H-score 100-199), and strong (H-score 200-300)) for both the cytoplasm and the membrane. The expression of Nectin-4 was compared between different histotypes by adopting the specific Nectin-4 score and Fisher's exact test. Nectin-4 membrane expression was positive in 14/89 (15.7%) GCTT components, with median H-score of 0 (range 0-120; IQR 0-10). Choriocarcinoma (CHC) (median H-score 29 (range 20-40, IQR 21.25-38.25)) and isolated syncytiotrophoblast cells (iSTCs) [median H-score 65 (range 0-90; IQR 10-147.5)) showed statistically significant higher Nectin-4 membrane expression than the other GCTT components (p < 0.001), with staining mostly observed in syncytiotrophoblasts in CHC and thus mirroring what found in "normal" syncytiotrophoblasts of placental tissue (adopted as positive control). Additionally, 2/4 (50%) post-chemotherapy metastatic recurrences (one Tpt and one YSTpt) and 3/25 (12%) EC showed positive weak Nectin-4 membrane expression. To summarize, our study reveals that only a small minority of GCTT exhibit positive weak Nectin-4 membrane expression. However, a subgroup of potentially aggressive GCTT (especially CHC and post-chemotherapy metastatic recurrences) more frequently exhibits Nectin-4 membrane expression, thus prompting future studies to assess whether these patients may be potentially eligible for EV therapy.
Virchows Archiv : an international journal of pathology. 2025 Sep 11 [Epub ahead of print]
Costantino Ricci, Francesca Ambrosi, Tania Franceschini, Alessia Grillini, Eugenia Franchini, Francesco Vasuri, Agnese Orsatti, Luisa Di Sciascio, Francesco Massari, Veronica Mollica, Andrea Marchetti, Federico Mineo Bianchi, Maurizio Colecchia, Andres Martin Acosta, João Lobo, Michelangelo Fiorentino
Pathology Unit, DIAP-Dipartimento Interaziendale Anatomia Patologica, Maggiore Hospital-AUSL Bologna, Bologna, Italy. ., Pathology Unit, DIAP-Dipartimento Interaziendale Anatomia Patologica, Maggiore Hospital-AUSL Bologna, Bologna, Italy., Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna, Italy., Pathology Unit, IRCCS Azienda Ospedaliero-Universitaria Di Bologna, Bologna, Italy., Urology Department, Maggiore Hospital-AUSL Bologna, Bologna, Italy., Department of Pathology, IRCCS San Raffaele Scientific Institute, Milan, Italy., Department of Pathology, Indiana University School of Medicine, Indianapolis, IN, USA., Department of Pathology, Portuguese Oncology Institute of Porto (IPOP), Porto, Portugal.
PubMed http://www.ncbi.nlm.nih.gov/pubmed/40936013