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Concordance of PD‐1 and PD‐L1 (B7‐H1) in paired primary and metastatic clear cell renal cell carcinoma

OBJECTIVES: Previous studies noted discordance of programmed death‐1 (PD‐1) and one of its ligands (PD‐L1) across patient‐matched primary and metastatic clear cell renal cell carcinoma (ccRCC). There are inconsistencies if the primary or metastatic tumor has higher expression, and whether metastatic...

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Autores principales: Eckel‐Passow, Jeanette E., Ho, Thai H., Serie, Daniel J., Cheville, John C., Houston Thompson, R., Costello, Brian A., Dong, Haidong, Kwon, Eugene D., Leibovich, Bradley C., Parker, Alexander S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6997072/
https://www.ncbi.nlm.nih.gov/pubmed/31829518
http://dx.doi.org/10.1002/cam4.2769
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author Eckel‐Passow, Jeanette E.
Ho, Thai H.
Serie, Daniel J.
Cheville, John C.
Houston Thompson, R.
Costello, Brian A.
Dong, Haidong
Kwon, Eugene D.
Leibovich, Bradley C.
Parker, Alexander S.
author_facet Eckel‐Passow, Jeanette E.
Ho, Thai H.
Serie, Daniel J.
Cheville, John C.
Houston Thompson, R.
Costello, Brian A.
Dong, Haidong
Kwon, Eugene D.
Leibovich, Bradley C.
Parker, Alexander S.
author_sort Eckel‐Passow, Jeanette E.
collection PubMed
description OBJECTIVES: Previous studies noted discordance of programmed death‐1 (PD‐1) and one of its ligands (PD‐L1) across patient‐matched primary and metastatic clear cell renal cell carcinoma (ccRCC). There are inconsistencies if the primary or metastatic tumor has higher expression, and whether metastatic tumor expression is associated with patient outcome. Thus, we examined PD‐1 and PD‐L1 in patient‐matched tumors using a large number of ccRCC patients with long follow‐up. MATERIALS AND METHODS: We analyzed PD‐1 and PD‐L1 using immunohistochemistry in patient‐matched primary and metastatic tumors from 110 ccRCC patients. Concordance was assessed among longitudinal metastatic tumors, as well as across patient‐matched primary and metastatic tumors. Cox proportional hazards regression was used to evaluate the associations of metastatic tumor expression with cancer‐specific survival. RESULTS: We observed inter‐metastatic tumor heterogeneity of PD‐1 in 25 (69%) of the 36 patients and of PD‐L1 in seven (19%) patients. Concordance between patient‐matched primary and metastatic tumors was 73% (Kappa = 0.16, 95% CI: −0.003‐0.32). Similarly, concordance of PD‐L1 between metastatic and patient‐matched primary tumors was 78% (Kappa = 0.27, 95% CI: 0.09‐0.46). Both markers demonstrated higher expression in primary vs metastatic tumors. Metastatic tumor expression of PD‐1 was significantly associated with metastatic location (P < .0001) and ccRCC‐specific survival (HR = 2.15, 95% CI: 1.06‐4.36, P = .035). CONCLUSIONS: The expression of PD‐1 and PD‐L1 is discordant across patient‐matched ccRCC tumors, with higher expression in primary tumors. Higher PD‐1 expression was associated with metastatic location and lower cancer‐specific survival. If validated, these results highlight the importance of evaluating these biomarkers in metastatic tissue specifically.
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spelling pubmed-69970722020-02-05 Concordance of PD‐1 and PD‐L1 (B7‐H1) in paired primary and metastatic clear cell renal cell carcinoma Eckel‐Passow, Jeanette E. Ho, Thai H. Serie, Daniel J. Cheville, John C. Houston Thompson, R. Costello, Brian A. Dong, Haidong Kwon, Eugene D. Leibovich, Bradley C. Parker, Alexander S. Cancer Med Cancer Biology OBJECTIVES: Previous studies noted discordance of programmed death‐1 (PD‐1) and one of its ligands (PD‐L1) across patient‐matched primary and metastatic clear cell renal cell carcinoma (ccRCC). There are inconsistencies if the primary or metastatic tumor has higher expression, and whether metastatic tumor expression is associated with patient outcome. Thus, we examined PD‐1 and PD‐L1 in patient‐matched tumors using a large number of ccRCC patients with long follow‐up. MATERIALS AND METHODS: We analyzed PD‐1 and PD‐L1 using immunohistochemistry in patient‐matched primary and metastatic tumors from 110 ccRCC patients. Concordance was assessed among longitudinal metastatic tumors, as well as across patient‐matched primary and metastatic tumors. Cox proportional hazards regression was used to evaluate the associations of metastatic tumor expression with cancer‐specific survival. RESULTS: We observed inter‐metastatic tumor heterogeneity of PD‐1 in 25 (69%) of the 36 patients and of PD‐L1 in seven (19%) patients. Concordance between patient‐matched primary and metastatic tumors was 73% (Kappa = 0.16, 95% CI: −0.003‐0.32). Similarly, concordance of PD‐L1 between metastatic and patient‐matched primary tumors was 78% (Kappa = 0.27, 95% CI: 0.09‐0.46). Both markers demonstrated higher expression in primary vs metastatic tumors. Metastatic tumor expression of PD‐1 was significantly associated with metastatic location (P < .0001) and ccRCC‐specific survival (HR = 2.15, 95% CI: 1.06‐4.36, P = .035). CONCLUSIONS: The expression of PD‐1 and PD‐L1 is discordant across patient‐matched ccRCC tumors, with higher expression in primary tumors. Higher PD‐1 expression was associated with metastatic location and lower cancer‐specific survival. If validated, these results highlight the importance of evaluating these biomarkers in metastatic tissue specifically. John Wiley and Sons Inc. 2019-12-12 /pmc/articles/PMC6997072/ /pubmed/31829518 http://dx.doi.org/10.1002/cam4.2769 Text en © 2019 The Authors. Cancer Medicine published by John Wiley & Sons Ltd. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Cancer Biology
Eckel‐Passow, Jeanette E.
Ho, Thai H.
Serie, Daniel J.
Cheville, John C.
Houston Thompson, R.
Costello, Brian A.
Dong, Haidong
Kwon, Eugene D.
Leibovich, Bradley C.
Parker, Alexander S.
Concordance of PD‐1 and PD‐L1 (B7‐H1) in paired primary and metastatic clear cell renal cell carcinoma
title Concordance of PD‐1 and PD‐L1 (B7‐H1) in paired primary and metastatic clear cell renal cell carcinoma
title_full Concordance of PD‐1 and PD‐L1 (B7‐H1) in paired primary and metastatic clear cell renal cell carcinoma
title_fullStr Concordance of PD‐1 and PD‐L1 (B7‐H1) in paired primary and metastatic clear cell renal cell carcinoma
title_full_unstemmed Concordance of PD‐1 and PD‐L1 (B7‐H1) in paired primary and metastatic clear cell renal cell carcinoma
title_short Concordance of PD‐1 and PD‐L1 (B7‐H1) in paired primary and metastatic clear cell renal cell carcinoma
title_sort concordance of pd‐1 and pd‐l1 (b7‐h1) in paired primary and metastatic clear cell renal cell carcinoma
topic Cancer Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6997072/
https://www.ncbi.nlm.nih.gov/pubmed/31829518
http://dx.doi.org/10.1002/cam4.2769
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