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Updated: May 11, 2026
Quantitation of Protein Expression and Co-localization Using Multiplexed Immuno-histochemical Staining and Multispectral Imaging
Published on: April 8, 2016
Nectin-4 Expression in Prostatic Adenocarcinoma: An Immunohistochemical Study
Ezra G Baraban1, Evangelia Vlachou2, Sunil Patel3
1Department of Pathology, Johns Hopkins Hospital, Baltimore, Maryland, USA.
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.
Insights
Nectin-4 protein is commonly found in both benign prostate tissue and prostate cancer, suggesting potential for enfortumab vedotin (EV) therapy in prostate cancer patients.
Area of Science:
- Oncology
- Urothelial Carcinoma Research
- Prostate Cancer Research
Background:
- Enfortumab vedotin (EV), a Nectin-4 targeted antibody drug conjugate, is a frontline therapy for urothelial carcinoma (UC).
- Nectin-4 is widely expressed in UC, driving its use in this cancer.
- Limited data exists on Nectin-4 expression in prostate cancer, despite many UC patients having concomitant prostate cancer.
Purpose of the Study:
- To investigate Nectin-4 protein expression in prostate cancer using immunohistochemistry.
- To determine if Nectin-4 expression levels differ across prostate cancer grades.
- To assess the potential for Nectin-4 targeted therapies in prostate cancer.
Main Methods:
- Immunohistochemistry was used to evaluate Nectin-4 expression in 302 prostatic adenocarcinomas (Grade Groups 1-5).
- Expression intensity was scored (1-3), and H-scores were calculated (percentage of cells x intensity).
- Nectin-4 expression in benign prostate tissue was also assessed for comparison.
Main Results:
- Nectin-4 was frequently expressed in benign prostate tissue (86%) and prostatic adenocarcinoma (91%).
- Mean Nectin-4 H-score was significantly higher in adenocarcinoma (90) than benign tissue (40) (p < 0.001).
- No significant differences in Nectin-4 expression were observed across prostate cancer Grade Groups 1-5.
Conclusions:
- Nectin-4 protein is commonly expressed in both benign prostate tissue and prostate adenocarcinoma.
- These findings support further investigation into enfortumab vedotin (EV) efficacy for prostate cancer.
- Nectin-4 expression provides a rationale for exploring EV in prostate cancer patients.
