gms | German Medical Science

Introduction: Nectin-4 plays a role in tumor proliferation, lymphangiogenesis, and angiogenesis, highlighting its potential as a therapy target for malignant tumors. Enfortumab Vedotin (EV), a Nektin-4 Antibody-drug-conjugate was recently approved for bladder cancer (BC). Limited data exist on nectin-4 expression in other urogenital tumors. Our study aims to investigate nectin-4 expression in surgical specimen tissue across different prostate cancer (PC) stages to predict the potential application of EV.

Methods: The study comprised 26 samples of benign prostate hyperplasia (BPH), organ-confined PC, and adjacent normal prostatic tissue obtained from 53 patients. Additionally, 32 samples from metastasized PC were analyzed. Tissue microarrays were created and samples were immunohistochemically stained for Nectin-4 expression. Nectin-4 expression intensity and distribution were microscopically evaluated using an established immunoreactivity score (0—300). Results were compared among tissue groups, PC progression lines, and clinical data.

Results: When comparing BPH with all PC tissues, median IRS of 101 and 88 were obtained (p=0.005). However, for BPH, adjacent normal prostatic tissue, cM0 and cM1 PC tissue, median values were 73, 110, 96 and 68, respectively (BPH vs. adjacent normal prostatic tissue, p=0.0001; cM0 vs. cM1, p=0.005). In PC ≤pT2c and ≥pT3b, median expression was 101 and 78, respectively (0.011) and pN0–pN1 showed median values of 94–68 (0.004).

Conclusions: PC seems to exhibit lower Nectin-4 expression in the early stages. However, all tissues in prostate cancer bearing prostate showed elevated Nectin-4 levels, as did normal prostatic tissue. Expression is substantially lower in advanced PCs. Expression patterns align with those observed in BC under comparable staining protocols.