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Expression of PD-L1 in triple-negative breast cancer based on different immunohistochemical antibodies
BACKGROUND: To date, there are no effective therapeutic targeting agents for triple-negative breast cancer (TNBC), and PD-L1 has presented potential as an effective marker of immunotherapeutic agents. The aim of this study was to evaluate the expression of PD-L1 by three different immunohistochemica...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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BioMed Central
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4902914/ https://www.ncbi.nlm.nih.gov/pubmed/27286842 http://dx.doi.org/10.1186/s12967-016-0925-6 |
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author | Sun, Woo Young Lee, Yu Kyung Koo, Ja Seung |
author_facet | Sun, Woo Young Lee, Yu Kyung Koo, Ja Seung |
author_sort | Sun, Woo Young |
collection | PubMed |
description | BACKGROUND: To date, there are no effective therapeutic targeting agents for triple-negative breast cancer (TNBC), and PD-L1 has presented potential as an effective marker of immunotherapeutic agents. The aim of this study was to evaluate the expression of PD-L1 by three different immunohistochemical antibodies in TNBC. METHODS: Interpretation of all three PD-L1 antibodies showed good concordance among three readers (kappa value >0.610) in both cancer cells and immune cells. Using a tissue microarray (TMA) constructed from 218 cases of TNBC, we performed immunohistochemical staining using three of the most popular commercially used PD-L1 monoclonal antibodies (clones 28-8, E1L3N and SP142) in cancer cells and immune cells. RESULTS: Using various cut-off values of previous studies (1, 5, 10 and 50 %), the expression rates in cancer cells were: PD-L1 (E1L3N) (14.7, 14.7, 11.0, 2.3 %), PD-L1 (28-8) (13.3, 12.4, 10.1, 1.8 %), and PD-L1 (SP142) (11.5, 11.0, 6.9, 0.5 %), respectively. At the 5 % cut-off value, the discordance rate among the three antibodies was 6.0–10.6 % and was highest between PD-L1 (SP142) and the other two antibodies. The expression rates in immune cells were PD-L1 (E1L3N) (37.6 %), PD-L1 (28-8) (36.7 %), and PD-L1 (SP142) (19.3 %), and the discordance rate among the three antibodies ranged from 13.8 to 24.8 % and was also highest between PD-L1 (SP142) and the other two antibodies. Among stromal histologic types, higher PD-L1 expression in cancer cells and immune cells was measured in inflammatory-type (p < 0.05). The absence of PD-L1 (28-8) staining in immune cells was associated with shorter disease free survival (DFS) and overall survival (OS) (p = 0.043, and p = 0.021) in univariate analyses, and with shorter OS in multivariate Cox analysis (hazard ratio: 5.429, 95 % CI 1.214–24.28, p = 0.027). CONCLUSIONS: PD-L1 detection in cancer cells and immune cells varied by antibody clone. The greatest amount of staining occurred with PD-L1 (E1L3N), followed by PD-L1 (28-8) and PD-L1 (SP142). The concordance rate among monoclonal PD-L1 antibodies was higher between PD-L1 (28-8) and PD-L1 (E1L3N). To determine the gold standard antibody and the most appropriate cut-off value, further study of the clinical trial group treated with PD-L1 inhibitor is necessary. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12967-016-0925-6) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-4902914 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-49029142016-06-12 Expression of PD-L1 in triple-negative breast cancer based on different immunohistochemical antibodies Sun, Woo Young Lee, Yu Kyung Koo, Ja Seung J Transl Med Research BACKGROUND: To date, there are no effective therapeutic targeting agents for triple-negative breast cancer (TNBC), and PD-L1 has presented potential as an effective marker of immunotherapeutic agents. The aim of this study was to evaluate the expression of PD-L1 by three different immunohistochemical antibodies in TNBC. METHODS: Interpretation of all three PD-L1 antibodies showed good concordance among three readers (kappa value >0.610) in both cancer cells and immune cells. Using a tissue microarray (TMA) constructed from 218 cases of TNBC, we performed immunohistochemical staining using three of the most popular commercially used PD-L1 monoclonal antibodies (clones 28-8, E1L3N and SP142) in cancer cells and immune cells. RESULTS: Using various cut-off values of previous studies (1, 5, 10 and 50 %), the expression rates in cancer cells were: PD-L1 (E1L3N) (14.7, 14.7, 11.0, 2.3 %), PD-L1 (28-8) (13.3, 12.4, 10.1, 1.8 %), and PD-L1 (SP142) (11.5, 11.0, 6.9, 0.5 %), respectively. At the 5 % cut-off value, the discordance rate among the three antibodies was 6.0–10.6 % and was highest between PD-L1 (SP142) and the other two antibodies. The expression rates in immune cells were PD-L1 (E1L3N) (37.6 %), PD-L1 (28-8) (36.7 %), and PD-L1 (SP142) (19.3 %), and the discordance rate among the three antibodies ranged from 13.8 to 24.8 % and was also highest between PD-L1 (SP142) and the other two antibodies. Among stromal histologic types, higher PD-L1 expression in cancer cells and immune cells was measured in inflammatory-type (p < 0.05). The absence of PD-L1 (28-8) staining in immune cells was associated with shorter disease free survival (DFS) and overall survival (OS) (p = 0.043, and p = 0.021) in univariate analyses, and with shorter OS in multivariate Cox analysis (hazard ratio: 5.429, 95 % CI 1.214–24.28, p = 0.027). CONCLUSIONS: PD-L1 detection in cancer cells and immune cells varied by antibody clone. The greatest amount of staining occurred with PD-L1 (E1L3N), followed by PD-L1 (28-8) and PD-L1 (SP142). The concordance rate among monoclonal PD-L1 antibodies was higher between PD-L1 (28-8) and PD-L1 (E1L3N). To determine the gold standard antibody and the most appropriate cut-off value, further study of the clinical trial group treated with PD-L1 inhibitor is necessary. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12967-016-0925-6) contains supplementary material, which is available to authorized users. BioMed Central 2016-06-10 /pmc/articles/PMC4902914/ /pubmed/27286842 http://dx.doi.org/10.1186/s12967-016-0925-6 Text en © The Author(s) 2016 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Sun, Woo Young Lee, Yu Kyung Koo, Ja Seung Expression of PD-L1 in triple-negative breast cancer based on different immunohistochemical antibodies |
title | Expression of PD-L1 in triple-negative breast cancer based on different immunohistochemical antibodies |
title_full | Expression of PD-L1 in triple-negative breast cancer based on different immunohistochemical antibodies |
title_fullStr | Expression of PD-L1 in triple-negative breast cancer based on different immunohistochemical antibodies |
title_full_unstemmed | Expression of PD-L1 in triple-negative breast cancer based on different immunohistochemical antibodies |
title_short | Expression of PD-L1 in triple-negative breast cancer based on different immunohistochemical antibodies |
title_sort | expression of pd-l1 in triple-negative breast cancer based on different immunohistochemical antibodies |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4902914/ https://www.ncbi.nlm.nih.gov/pubmed/27286842 http://dx.doi.org/10.1186/s12967-016-0925-6 |
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