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 journalArticle

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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

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Prostatic Neoplasms
Ligands
Programmed Cell Death 1 Receptor
Adenocarcinoma
Small Cell Carcinoma
Mortality
Antibodies
Proteins
Biomarkers
Immunohistochemistry
Staining and Labeling
Neoplasm Metastasis
Therapeutics

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Comprehensive Evaluation of Programmed Death-Ligand 1 Expression in Primary and Metastatic Prostate Cancer. / Haffner, Michael C.; Guner, Gunes; Taheri, Diana; Netto, George J.; Palsgrove, Doreen N.; Zheng, Qizhi; Guedes, Liana Benevides; Kim, Kunhwa; Tsai, Harrison; Esopi, David M.; Lotan, Tamara L.; Sharma, Rajni; Meeker, Alan K.; Chinnaiyan, Arul M.; Nelson, William G.; Yegnasubramanian, Srinivasan; Luo, Jun; Mehra, Rohit; Antonarakis, Emmanuel S.; Drake, Charles G.; De Marzo, Angelo M.

In: American Journal of Pathology, Vol. 188, No. 6, 06.2018, p. 1478-1485.

Research output: Contribution to journalArticle

Haffner, MC, Guner, G, Taheri, D, Netto, GJ, Palsgrove, DN, Zheng, Q, Guedes, LB, Kim, K, Tsai, H, Esopi, DM, Lotan, TL, Sharma, R, Meeker, AK, Chinnaiyan, AM, Nelson, WG, Yegnasubramanian, S, Luo, J, Mehra, R, Antonarakis, ES, Drake, CG & De Marzo, AM 2018, 'Comprehensive Evaluation of Programmed Death-Ligand 1 Expression in Primary and Metastatic Prostate Cancer', American Journal of Pathology, vol. 188, no. 6, pp. 1478-1485. https://doi.org/10.1016/j.ajpath.2018.02.014
Haffner, Michael C. ; Guner, Gunes ; Taheri, Diana ; Netto, George J. ; Palsgrove, Doreen N. ; Zheng, Qizhi ; Guedes, Liana Benevides ; Kim, Kunhwa ; Tsai, Harrison ; Esopi, David M. ; Lotan, Tamara L. ; Sharma, Rajni ; Meeker, Alan K. ; Chinnaiyan, Arul M. ; Nelson, William G. ; Yegnasubramanian, Srinivasan ; Luo, Jun ; Mehra, Rohit ; Antonarakis, Emmanuel S. ; Drake, Charles G. ; De Marzo, Angelo M. / Comprehensive Evaluation of Programmed Death-Ligand 1 Expression in Primary and Metastatic Prostate Cancer. In: American Journal of Pathology. 2018 ; Vol. 188, No. 6. pp. 1478-1485.
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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.",
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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.

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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.

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