BACKGROUND: The Nectin-4 directed antibody drug conjugate enfortumab vedotin (EV) has emerged as frontline systemic therapy in combination with immune checkpoint blockade for urothelial carcinoma (UC), capitalizing on the ubiquitous expression of this protein in UC. There is limited data available regarding expression of Nectin-4 by immunohistochemistry in prostate cancer, but this is of interest as a substantial number of UC patients likely to receive EV have concomitant prostate cancer. METHODS: Nectin-4 protein expression was evaluated by immunohistochemistry in tissue microarrays encompassing a cohort of 302 prostatic adenocarcinomas spanning Grade Groups 1-5. Intensity of expression was scored from 1 (weak) to 3 (intense staining readily apparent at low magnification). H-scores were calculated by multiplying the percentage of cells staining by the intensity of expression. RESULTS: Nectin-4 expression was frequently observed in benign prostate tissue (86% of cases, mean H-score of 40, median 20, interquartile range [IQR]: 10-60) and in prostatic adenocarcinoma (91% of cases, mean H-score of 90, median 70, IQR: 20-150). Significant differences in Nectin-4 expression among prostatic adenocarcinoma Grade Groups 1-5 were not observed. Across all prostatic adenocarcinomas evaluated, the mean Nectin-4 H-score of 90 was statistically significantly higher than the mean H-score of 40 observed in benign prostate tissue (p <
0.001). Three of four prostatic ductal adenocarcinomas showed Nectin-4 expression, with a median H-score of 250 (IQR: 152-300). CONCLUSIONS: Nectin-4 protein expression is common in benign prostate tissue and prostatic adenocarcinoma. These findings provide a rationale for future studies investigating potential activity of EV in prostate cancer.