Baraban Ezra G, Vlachou Evangelia, Patel Sunil, Kates Max, Johnson Burles, Smith Armine, Shenderov Eugene, Sharma Shivang, Denmeade Samuel R, Brame Alex, Han Misop, De Marzo Angelo M, Matoso Andres, Hoffman-Censits Jean
Department of Pathology, Johns Hopkins Hospital, Baltimore, Maryland, USA.
Department of Medical Oncology, Johns Hopkins Hospital, Baltimore, Maryland, USA.
Prostate. 2025 Apr;85(5):443-447. doi: 10.1002/pros.24846. Epub 2025 Jan 2.
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.
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.
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).
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.
Nectin-4导向的抗体药物偶联物安罗替尼（EV）已成为尿路上皮癌（UC）一线全身治疗方案，与免疫检查点阻断联合使用，利用该蛋白在UC中的普遍表达。关于免疫组化检测前列腺癌中Nectin-4表达的数据有限，但鉴于大量可能接受EV治疗的UC患者同时患有前列腺癌，这一点值得关注。
通过免疫组化评估302例1-5级前列腺腺癌组织微阵列中Nectin-4蛋白的表达。表达强度从1（弱）到3（低倍镜下即可明显看到强染色）进行评分。H评分通过将染色细胞的百分比乘以表达强度来计算。
在良性前列腺组织（86%的病例，平均H评分为40，中位数为20，四分位间距[IQR]：10-60）和前列腺腺癌（91%的病例，平均H评分为90，中位数为70，IQR：20-150）中经常观察到Nectin-4表达。未观察到前列腺腺癌1-5级组之间Nectin-4表达的显著差异。在所有评估的前列腺腺癌中，Nectin-4的平均H评分为90，在统计学上显著高于良性前列腺组织中观察到的平均H评分40（p<0.001）。四例前列腺导管腺癌中有三例显示Nectin-4表达，中位数H评分为250（IQR：152-300）。
Nectin-4蛋白表达在良性前列腺组织和前列腺腺癌中很常见。这些发现为未来研究EV在前列腺癌中的潜在活性提供了理论依据。
