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New Insights into Nectin-4 Expression in Testicular Choriocarcinoma and Its Potential Treatment with Enfortumab Vedotin: Analysis of a Multi-Institutional Series and Association with Clinical-Pathological Features - Beyond the Abstract

Choriocarcinoma (CHC) is an aggressive subtype of germ cell tumors of the testis (GCTT). It is characterized by advanced stage and distant metastases at onset, hemorrhagic complications, elevated β-hCG levels, and a 3-year survival rate of 20% (with combined chemotherapy regimens).

Enfortumab vedotin (EV), an antibody-drug conjugate (ADC) that targets Nectin-4 (whose expression is a prerequisite for therapeutic response to EV), has been shown to improve overall survival in patients with metastatic urothelial carcinoma. Two recent studies found that CHC exhibits Nectin-4 expression, thus suggesting that EV could be a promising therapeutic option for this aggressive tumor. Nevertheless, the number of examined cases was limited and exhibited significant heterogeneity (both female and male subjects, as well as both gestational and non-gestational CHCs), without analyzing the correlation between Nectin-4 expression and clinical-pathological features.

In this study, we found that: a) Nectin-4 cytoplasmatic expression was positive in 17/20 (85%) primary CHCs, and was associated with higher % of CHC (p=0.028) and β-HCG serum levels (p=0.007), whit moderate/strong expression associated with lower age at diagnosis (p=0.0039); b) Nectin-4 membrane expression was positive in 16/20 (80%) primary CHCs, but it did not show statistically significant associations with the analyzed variables, c) The only post-chemotherapy, metastatic, and pure CHC exhibited the highest Nectin-4 membrane expression (H-score: 155), showing higher membrane expression if compared to its paired primary tumor (H-score: 33).

In summary, the results of the present study suggest that, considering this specific clinical scenario (aggressive tumor in young men and with limited therapeutic options), Nectin-4 expression and the potential EV's efficacy in testicular CHC need to be investigated in the future.

Written by: Costantino Ricci,1 Luisa Di Sciascio,2,3 Francesca Ambrosi,1,2 Agnese Orsatti,1 Alessia Grillini,1 Eugenia Franchini,1 Veronica Mollica,4 Francesco Massari,2,4 Federico Mineo Bianchi,5 Francesco Vasuri,2,6 João Lobo,7,8,9 Nuno Tiago Tavares,8,10 Fernanda Fernandes-Pontes,8,10 Andres Martin Acosta,11 Michelangelo Fiorentino,1,2

  1. Pathology Unit, DIAP-Dipartimento Interaziendale Di Anatomia Patologica Di Bologna, Maggiore Hospital-AUSL Bologna, Via Dell'Ospedale 8, 40133, Bologna, Italy.
  2. Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna, Italy.
  3. Pathology Unit, IRCCS Azienda Ospedaliero-Universitaria Di Bologna, Bologna, Italy.
  4. Medical Oncology, IRCCS Azienda Ospedaliero, Universitaria Di Bologna, Bologna, Italy.
  5. Urology Department, Maggiore Hospital-AUSL Bologna, Bologna, Italy.
  6. Pathology Unit, Santa Maria Delle Croci Hospital, Ravenna, Italy.
  7. Department of Pathology, Portuguese Oncology Institute of Porto (IPOP), Porto, Portugal.
  8. 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.
  9. Department of Pathology and Molecular Immunology, ICBAS-School of Medicine and Biomedical Sciences, University of Porto (ICBAS-UP), Porto, Portugal.
  10. Doctoral Programme in Biomedical Sciences, ICBAS-School of Medicine and Biomedical Sciences, University of Porto (ICBAS-UP), Porto, Portugal.
  11. Department of Pathology, Indiana University School of Medicine, Indianapolis, USA.
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