Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins School of Medicine, Baltimore, Maryland; Department of Pathology, The Johns Hopkins School of Medicine, Baltimore, Maryland.
Department of Pathology, The Johns Hopkins School of Medicine, Baltimore, Maryland.
Am J Pathol. 2018 Jun;188(6):1478-1485. doi: 10.1016/j.ajpath.2018.02.014. Epub 2018 Mar 22.
Antibodies targeting the programmed cell death protein 1/programmed death-ligand 1 (PD-L1) interaction have shown clinical activity in multiple cancer types. PD-L1 protein expression is a clinically validated predictive biomarker of response for such therapies. Prior studies evaluating the expression of PD-L1 in primary prostate cancers have reported highly variable rates of PD-L1 positivity. In addition, limited data exist on PD-L1 expression in metastatic castrate-resistant prostate cancer (mCRPC). Here, we determined PD-L1 protein expression by immunohistochemistry using a validated PD-L1-specific antibody (SP263) in a large and representative cohort of primary prostate cancers and prostate cancer metastases. The study included 539 primary prostate cancers comprising 508 acinar adenocarcinomas, 24 prostatic duct adenocarcinomas, 7 small-cell carcinomas, and a total of 57 cases of mCRPC. PD-L1 positivity was low in primary acinar adenocarcinoma, with only 7.7% of cases showing detectable PD-L1 staining. Increased levels of PD-L1 expression were noted in 42.9% of small-cell carcinomas. In mCRPC, 31.6% of cases showed PD-L1-specific immunoreactivity. In conclusion, in this comprehensive evaluation of PD-L1 expression in prostate cancer, PD-L1 expression is rare in primary prostate cancers, but increased rates of PD-L1 positivity were observed in mCRPC. These results will be important for the future clinical development of programmed cell death protein 1/PD-L1-targeting therapies in prostate cancer.
针对程序性细胞死亡蛋白 1/程序性死亡配体 1（PD-L1）相互作用的抗体在多种癌症类型中显示出临床活性。PD-L1 蛋白表达是此类治疗反应的临床验证预测生物标志物。先前评估原发性前列腺癌中 PD-L1 表达的研究报告了 PD-L1 阳性率高度可变。此外，转移性去势抵抗性前列腺癌（mCRPC）中 PD-L1 表达的数据有限。在这里，我们使用经过验证的 PD-L1 特异性抗体（SP263）通过免疫组织化学测定了大量代表性原发性前列腺癌和前列腺癌转移中的 PD-L1 蛋白表达。该研究包括 539 例原发性前列腺癌，其中包括 508 例腺泡腺癌、24 例前列腺导管腺癌、7 例小细胞癌和总共 57 例 mCRPC。原发性腺泡腺癌中的 PD-L1 阳性率较低，只有 7.7%的病例显示可检测到 PD-L1 染色。小细胞癌中观察到 PD-L1 表达水平增加，有 42.9%的病例出现。在 mCRPC 中，31.6%的病例显示 PD-L1 特异性免疫反应。总之，在这项对前列腺癌中 PD-L1 表达的综合评估中，原发性前列腺癌中 PD-L1 表达罕见，但在 mCRPC 中观察到 PD-L1 阳性率增加。这些结果对于未来前列腺癌中程序性细胞死亡蛋白 1/PD-L1 靶向治疗的临床发展将非常重要。
