Topographical and stage-related expression of nectin-4 in prostate cancer.

Introduction: 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. Material and methods: 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. Results: 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). Conclusions: 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.