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ArticleVirchows Archiv : an international journal of pathology2026

Immunohistochemical expression of Nectin-4 and potential implications for enfortumab vedotin therapy in germ cell tumors of the testis: a preliminary study.

Costantino Ricci, Francesca Ambrosi, Tania Franceschini, Alessia Grillini, Eugenia Franchini, Francesco Vasuri, Agnese Orsatti, Luisa Di Sciascio, Francesco Massari, Veronica Mollica and 6 more

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Article in Virchows Archiv : an international journal of pathology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed.

  1. Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

16 authors.

Costantino RicciPathology Unit, DIAP-Dipartimento Interaziendale Anatomia Patologica, Maggiore Hospital-AUSL Bologna, Bologna, Italy. costantino.ricci4@unibo.it.ORCID http://orcid.org/0000-0001-7254-4195
Francesca AmbrosiPathology Unit, DIAP-Dipartimento Interaziendale Anatomia Patologica, Maggiore Hospital-AUSL Bologna, Bologna, Italy.ORCID http://orcid.org/0000-0001-9046-1115
Tania FranceschiniPathology Unit, DIAP-Dipartimento Interaziendale Anatomia Patologica, Maggiore Hospital-AUSL Bologna, Bologna, Italy.ORCID http://orcid.org/0000-0003-2897-7756
Alessia GrilliniPathology Unit, DIAP-Dipartimento Interaziendale Anatomia Patologica, Maggiore Hospital-AUSL Bologna, Bologna, Italy.
Eugenia FranchiniPathology Unit, DIAP-Dipartimento Interaziendale Anatomia Patologica, Maggiore Hospital-AUSL Bologna, Bologna, Italy.
Francesco VasuriDepartment of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna, Italy.ORCID http://orcid.org/0000-0002-1145-6025
Agnese OrsattiPathology Unit, IRCCS Azienda Ospedaliero-Universitaria Di Bologna, Bologna, Italy.ORCID http://orcid.org/0009-0005-8560-1925
Luisa Di SciascioDepartment of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna, Italy.ORCID http://orcid.org/0000-0003-1809-3826
Francesco MassariDepartment of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna, Italy.ORCID http://orcid.org/0000-0001-6476-6871
Veronica MollicaDepartment of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna, Italy.ORCID http://orcid.org/0000-0002-5169-3631
Andrea MarchettiDepartment of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna, Italy.ORCID http://orcid.org/0000-0001-7892-9619
Federico Mineo BianchiUrology Department, Maggiore Hospital-AUSL Bologna, Bologna, Italy.ORCID http://orcid.org/0000-0003-3331-0374
Maurizio ColecchiaDepartment of Pathology, IRCCS San Raffaele Scientific Institute, Milan, Italy.ORCID http://orcid.org/0000-0003-1914-0743
Andres Martin AcostaDepartment of Pathology, Indiana University School of Medicine, Indianapolis, IN, USA.ORCID http://orcid.org/0000-0003-0164-5911
João LoboDepartment of Pathology, Portuguese Oncology Institute of Porto (IPOP), Porto, Portugal.ORCID http://orcid.org/0000-0001-6829-1391
Michelangelo FiorentinoPathology Unit, DIAP-Dipartimento Interaziendale Anatomia Patologica, Maggiore Hospital-AUSL Bologna, Bologna, Italy.ORCID http://orcid.org/0000-0002-1749-150X

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

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.

Indexed as

Antibodies, MonoclonalBiomarkers, TumorCell Adhesion MoleculesNeoplasms, Germ Cell and EmbryonalTesticular NeoplasmsAdolescentAdultHumansImmunohistochemistryMaleMiddle AgedNectinsYoung AdultAntibodies, MonoclonalBiomarkers, TumorCell Adhesion Moleculesenfortumab vedotinNECTIN4 protein, humanNectinsAntibody–drug conjugatesChoriocarcinomaEnfortumab vedotinGerm cell tumors of the testisNectin-4

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.