26nrwgu09
10.3205/26nrwgu09
urn:nbn:de:0183-26nrwgu095
Meeting Abstract
NECTIN4 amplification is a frequent event in central nervous system metastases of urothelial carcinoma
Weiten
Weiten
Richard
R
University Hospital Cologne, Germany, Department of Urology, Uro-Oncology, Robot-Assisted and Specialized Urologic Surgery, Cologne, Deutschland
author
Rieger
Rieger
Constantin
C
University Hospital Cologne, Germany, Department of Urology, Uro-Oncology, Robot-Assisted and Specialized Urologic Surgery, Cologne, Deutschland
author
Heidenreich
Heidenreich
Julian
J
University Hospital Cologne, Germany, Department of Urology, Uro-Oncology, Robot-Assisted and Specialized Urologic Surgery, Cologne, Deutschland
author
Tolkach
Tolkach
Yuri
Y
University Hospital Cologne, Germany, Institute of Pathology, Cologne, Deutschland
author
Stehle
Stehle
Thomas
T
University Hospital Cologne, Germany, Institute of Neuropathology, Cologne, Deutschland
author
Schmid
Schmid
Florian
F
University Hospital Cologne, Germany, Department of Urology, Uro-Oncology, Robot-Assisted and Specialized Urologic Surgery, Cologne, Deutschland
University Hospital Zurich, Department of Urology, Zurich, Schweiz
author
Schmidt
Schmidt
Teresa
T
University Hospital Essen, Division of Clinical Neuro-Oncology, Department of Neurology and Center for Translational Neuro- and Behavioral Sciences (C-TNBS), Essen, Deutschland
author
Glase
Glase
Martin
M
St. Marien Hospital, Department of Neurology and Neurooncology, Lünen, Deutschland
University Hospital Bonn, University of Bonn, Department of Neurooncology, Center for Neurology, Bonn, Deutschland
author
Blau
Blau
Tobias
T
University Hospital Essen, Institute of Neuropathology, Essen, Deutschland
author
Keyvani
Keyvani
Kathy
K
University Hospital Essen, Institute of Neuropathology, Essen, Deutschland
author
Büttner
Büttner
Thomas
T
University Hospital Bonn, Department of Urology and Paediatric Urology, Bonn, Deutschland
author
Grünwald
Grünwald
Viktor
V
University Hospital Essen, Clinic for Internal Medicine (Tumor Research) and Clinic for Urology, Interdisciplinary Genitourinary Oncology at the West-German Cancer Center, Essen, Deutschland
author
Hölzel
Hölzel
Michael
M
University Hospital Bonn, Institute of Experimental Oncology, Bonn, Deutschland
author
Heidenreich
Heidenreich
Axel
A
University Hospital Cologne, Germany, Department of Urology, Uro-Oncology, Robot-Assisted and Specialized Urologic Surgery, Cologne, Deutschland
author
Eckstein
Eckstein
Markus
M
University Hospital Erlangen, Institute of Pathology , Erlangen, Deutschland
author
Klümper
Klümper
Niklas
N
University Hospital Bonn, Department of Urology and Paediatric Urology, Bonn, Deutschland
University Hospital Bonn, Institute of Experimental Oncology, Bonn, Deutschland
author
German Medical Science GMS Publishing House
Düsseldorf
610
20260408
engl
This is an Open Access article distributed under the terms of the Creative Commons Attribution 4.0 License.
Dieser Artikel ist ein Open-Access-Artikel und steht unter den Lizenzbedingungen der Creative Commons Attribution 4.0 License (Namensnennung).
M0643
09
Nordrhein-Westfälische Gesellschaft für Urologie e.V.
71. Kongress der Nordrhein-Westfälischen Gesellschaft für Urologie
Paul-Mellin Sitzung I
Essen
20260416
20260417
V 1.9
TextIntroduction & objectives: NECTIN4 amplification has emerged as a promising biomarker for predicting response to targeted anti-NECTIN4 therapies in metastatic urothelial carcinoma (mUC), triple-negative breast cancer (TNBC), and non-small cell lung cancer (NSCLC). The anti-NECTIN4 antibody-drug conjugate enfortumab vedotin (EV), combined with pembrolizumab (EV/P), is now standard care for mUC. However, data on its effectiveness in patients with active central nervous system (CNS) metastases (MET) are limited, as these patients were excluded from pivotal trials. Recent studies show that NECTIN4 amplification is frequent in mUC (about 15–25%) and predicts response to EV and survival benefits. Furthermore, NECTIN4 amplification appears to be a stable genomic event during metastasis progression. This study aimed to characterize NECTIN4 amplification and protein expression specifically in CNS metastases of mUC compared with extracranial metastatic sites.Materials & methods: NECTIN4 gene amplification was assessed by fluorescence in situ hybridization (FISH), and tumors with a NECTIN4/CEN1 ratio ≥ 2.0 were classified as amplified. NECTIN4 protein expression was evaluated by immunohistochemistry (H-score). Statistical analyses were performed using nonparametric tests (Chi-square, Mann-Whitney U).Results: In our CNS MET cohort (n = 18), compared to previous comprehensive mUC cohorts (1: non-CNS mUC, n = 128; 2: EV-treated mUC, n = 108), NECTIN4 gene amplification was found in 66.7% of CNS MET cases (12/18), which is significantly higher than the 26% observed in the EV-treated cohort at baseline (28/108; Chi-square test, p = 0.0016). Additionally, CNS MET showed higher membranous NECTIN4 expression (median H-score 175, IQR 88–260) compared to non-CNS mUC (median H-score 40, IQR 0–140; p < 0.0001).Conclusion: In conclusion, NECTIN4 amplification is highly prevalent in CNS MET from UC. These results provide a strong biological rationale for extending the use of NECTIN4-targeted therapies such as EV to patients with brain MET.
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