TY - JOUR
T1 - Comprehensive Evaluation of Programmed Death-Ligand 1 Expression in Primary and Metastatic Prostate Cancer
AU - Haffner, Michael C.
AU - Guner, Gunes
AU - Taheri, Diana
AU - Netto, George J.
AU - Palsgrove, Doreen N.
AU - Zheng, Qizhi
AU - Guedes, Liana Benevides
AU - Kim, Kunhwa
AU - Tsai, Harrison
AU - Esopi, David M.
AU - Lotan, Tamara L.
AU - Sharma, Rajni
AU - Meeker, Alan K.
AU - Chinnaiyan, Arul M.
AU - Nelson, William G.
AU - Yegnasubramanian, Srinivasan
AU - Luo, Jun
AU - Mehra, Rohit
AU - Antonarakis, Emmanuel S.
AU - Drake, Charles G.
AU - De Marzo, Angelo M.
N1 - 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
PY - 2018/6
Y1 - 2018/6
N2 - 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.
AB - 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.
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U2 - 10.1016/j.ajpath.2018.02.014
DO - 10.1016/j.ajpath.2018.02.014
M3 - Article
C2 - 29577933
AN - SCOPUS:85047136400
SN - 0002-9440
VL - 188
SP - 1478
EP - 1485
JO - American Journal of Pathology
JF - American Journal of Pathology
IS - 6
ER -
