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

Michael C. Haffner, Gunes Guner, Diana Taheri, George J. Netto, Doreen N. Palsgrove, Qizhi Zheng, Liana Benevides Guedes, Kunhwa Kim, Harrison Tsai, David M. Esopi, Tamara L. Lotan, Rajni Sharma, Alan K. Meeker, Arul M. Chinnaiyan, William G. Nelson, Srinivasan Yegnasubramanian, Jun Luo, Rohit Mehra, Emmanuel S. Antonarakis, Charles G. DrakeAngelo M. De Marzo

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)1478-1485
Number of pages8
JournalAmerican Journal of Pathology
Volume188
Issue number6
DOIs
StatePublished - Jun 2018
Externally publishedYes

Bibliographical note

Funding Information:
Disclosures: C.G.D. has served as a paid consultant to Roche Genentech, Merck, and Novartis, and has received sponsored research funding from the Bristol Myers Squibb International Immuno-Oncology Network and Janssen, Inc.; A.M.D.M. has received sponsored research funding from Janssen, Inc., and has served as a paid consultant for Myriad Genetics and Cepheid, Inc.; T.L.L. has received research funds from Ventana; and E.S.A. is a paid consultant/advisor to Janssen, Astellas, Sanofi, Dendreon, Medivation, ESSA, AstraZeneca, Clovis, and Merck, has received research funding to his institution for clinical trials that he was directly involved in from Janssen, Johnson & Johnson, Sanofi, Dendreon, Genentech, Novartis, Tokai, Bristol Myers-Squibb, AstraZeneca, Clovis, and Merck, and is the co-inventor of biomarker technology that has been licensed to Qiagen.

Funding Information:
Supported in part by National Cancer Institute /NIH grants P50CA058236 (W.G.N., S.Y., A.M.D.M.), U01 CA196390 (S.Y., A.M.D.M.), CCSG P30CA006973 (T.L.L., A.K.M., W.G.N., S.Y., E.S.A., A.M.D.M.), US Department of Defense Prostate Cancer Research Program (PCRP) W81XWH-14-2-0182, The Prostate Cancer Biorepository Network (A.M.D.M.), a Prostate Cancer Foundation Challenge Award (S.Y., C.G.D.), and the Commonwealth Foundation (S.Y.).

Publisher Copyright:
© 2018 American Society for Investigative Pathology

Fingerprint

Dive into the research topics of 'Comprehensive Evaluation of Programmed Death-Ligand 1 Expression in Primary and Metastatic Prostate Cancer'. Together they form a unique fingerprint.

Cite this