Nectin-4 is a cell-adhesion molecule overexpressed in several malignancies and is a promising therapeutic target. Its expression profile and clinical relevance in prostate cancer (PCa) remain insufficiently defined.
This retrospective study at a single tertiary referral center included 111 surgical specimens: 85 from patients with PCa (53 non-metastatic radical prostatectomy; 32 metastatic transurethral resection of the prostate) and 26 from patients without PCa (19 benign prostatic hyperplasia [BPH] procedures; 7 cystoprostatectomies). Tissue microarrays were constructed. Nectin-4 immunohistochemistry was scored using an H-score (0-300). Comparisons were performed across predefined tissue groups and clinicopathologic strata using non-parametric tests.
Adjacent benign prostate showed higher median H-scores than PCa cores (101 vs 88; p = 0.008). Expression declined with pathological stage (≤pT2c vs ≥pT3a: 101 vs 78; p = 0.011) and with nodal involvement (pN0 vs pN1: 94 vs 68; p = 0.004). By subgroup, median H-scores were: BPH 73, tissue distant from PCa 105, tissue adjacent to PCa 116, non-metastatic PCa 96, and metastatic PCa 68 (p <0.0001; BPH vs adjacent p = 0.0001; M0 vs M1 p = 0.005). No difference was observed between hormone-sensitive and castration-resistant metastatic disease (73 vs 68; p = 0.34).
Nectin-4 expression in the prostate is heterogeneous and context-dependent, with higher levels in benign glands within cancer-bearing prostates and lower levels with advancing tumor stage and nodal/metastatic spread. These findings provide an expression map of nectin 4 across benign and malignant prostate compartments and disease stages and may inform future exploratory enrichment strategies for nectin-4-targeted therapies.
Central European journal of urology. 2026 Mar 22 [Epub]
Radion Garaz, Jörg Hennenlotter, Veronika Bahlinger, Tilman Todenhöfer, Arnulf Stenzl, Igor Tsaur, Steffen Rausch
Department of Urology, Eberhard Karls University of Tübingen, Germany., Institute of Pathology, University Hospital Tübingen, Germany., Studienpraxis Urologie, Nürtingen, Germany.