Comprehensive Evaluation of Programmed Death-Ligand 1 Expression in Primary and Metastatic Prostate Cancer

Abstract

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.

Figure 1

Validation of programmed death-ligand 1 (PD-L1) antibody used in the study. A: Integrated in silico analysis of NCI60 cell lines shows high-level PD-L1 expression in the lymphoblastic cell line SR and absence of PD-L1 expression in the renal cell carcinoma cell line SN12C. B: Western blot analysis of placental tissue lysate and SR and SN12C cell line lysates probed with anti–PD-L1 (SP263) shows immunoreactivity only in the predicted molecular weight range of PD-L1. C: Formalin-fixed, paraffin-embedded SN12C and SR cells show absence and strong membranous immunoreactivity for PD-L1, respectively. IHC, immunohistochemistry. Original magnification, ×20. WB, western blot.

Figure 2

Summary of observed programmed death-ligand 1 (PD-L1) immunoreactivity in primary and metastatic prostate cancer. A: Bar graph showing relative frequency (%) of lesions with detectable PD-L1 expression. B: Representative micrograph of primary prostate carcinoma showing no PD-L1 expression. C and D: Representative micrograph of metastatic prostate cancer with moderate- and high-level PD-L1 expression. E: Focal immunoreactivity in benign atrophic prostate epithelium associated with chronic inflammatory infiltrate. Original magnification, ×20 (B–E).