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PD-L1 expression and the prognostic significance in gastric cancer: a retrospective comparison of three PD-L1 antibody clones (SP142, 28–8 and E1L3N)
BACKGROUND: Immunohistochemistry (IHC) for programmed cell death ligand 1 (PD-L1) displays staining diversity. We compared IHC staining of PD-L1 in gastric cancer (GC) by using three commercially available antibody clones, and analyzed the correlation with the prognosis. METHODS: IHC using PD-L1 ant...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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BioMed Central
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6249875/ https://www.ncbi.nlm.nih.gov/pubmed/30463584 http://dx.doi.org/10.1186/s13000-018-0766-0 |
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author | Ma, Jing Li, Jianhui Qian, Meirui Han, Weili Tian, Miaomiao Li, Zengshan Wang, Zhe He, Shuixiang Wu, Kaichun |
author_facet | Ma, Jing Li, Jianhui Qian, Meirui Han, Weili Tian, Miaomiao Li, Zengshan Wang, Zhe He, Shuixiang Wu, Kaichun |
author_sort | Ma, Jing |
collection | PubMed |
description | BACKGROUND: Immunohistochemistry (IHC) for programmed cell death ligand 1 (PD-L1) displays staining diversity. We compared IHC staining of PD-L1 in gastric cancer (GC) by using three commercially available antibody clones, and analyzed the correlation with the prognosis. METHODS: IHC using PD-L1 antibodies (clones SP142, 28–8 and E1L3N) in 315 formalin-fixed paraffin-embedded samples was qualitatively compared at the 1, 5 and 10% cut-off by two pathologists on total, tumor and immune/stromal cells. We used computer – assisted scoring to quantitatively analyze and compare the “H-score” of PD-L1 expression in 66 samples on total cells. The antibody clone SP142 was selected to investigate the infiltration of PD-L1(+)CD8(+) T cells using automated quantitative immunofluorescence analyses (n = 50) and the prognostic significance. The prognoses were assessed by log-rank test. RESULTS: PD-L1 clones SP142 and 28–8 displayed great concordance by qualitative (κ = 0.816, 0.810 for total cells and tumor cells at the 5% cut-off) and quantitative analyses (R(2) = 0.7991, 0.8187 for positive percentage and “H-score”). PD-L1 clone SP142 showed the highest positivity in immune/stromal cells staining (18.41%) compared to 28–8 (7.62%), while clone E1L3N showed poor staining in both tumor and immune/stromal cells. Clone SP142, but not 28–8 and E1L3N, predicted a worse prognosis at the 5% cut-off (p = 0.0243). Both the clone SP142 and 28–8 had high inter-pathologist correlation for tumor staining (R(2) = 0.9805 and R(2) = 0.9853), but a moderate correlation for stromal/immune cell staining (R(2) = 0.5653 and R(2) = 0.5745). Furthermore, a higher density of PD-L1(+)CD8(+) T cells was correlated with a shorter survival time (R(2) = 0.0909, p = 0.0352). CONCLUSIONS: PD-L1 antibody clone SP142 was superior in cell staining, particularly in immune/stromal cell and prognosis. These findings are important for selection of PD-L1 antibody clones in the future diagnostic test. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13000-018-0766-0) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-6249875 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-62498752018-11-26 PD-L1 expression and the prognostic significance in gastric cancer: a retrospective comparison of three PD-L1 antibody clones (SP142, 28–8 and E1L3N) Ma, Jing Li, Jianhui Qian, Meirui Han, Weili Tian, Miaomiao Li, Zengshan Wang, Zhe He, Shuixiang Wu, Kaichun Diagn Pathol Research BACKGROUND: Immunohistochemistry (IHC) for programmed cell death ligand 1 (PD-L1) displays staining diversity. We compared IHC staining of PD-L1 in gastric cancer (GC) by using three commercially available antibody clones, and analyzed the correlation with the prognosis. METHODS: IHC using PD-L1 antibodies (clones SP142, 28–8 and E1L3N) in 315 formalin-fixed paraffin-embedded samples was qualitatively compared at the 1, 5 and 10% cut-off by two pathologists on total, tumor and immune/stromal cells. We used computer – assisted scoring to quantitatively analyze and compare the “H-score” of PD-L1 expression in 66 samples on total cells. The antibody clone SP142 was selected to investigate the infiltration of PD-L1(+)CD8(+) T cells using automated quantitative immunofluorescence analyses (n = 50) and the prognostic significance. The prognoses were assessed by log-rank test. RESULTS: PD-L1 clones SP142 and 28–8 displayed great concordance by qualitative (κ = 0.816, 0.810 for total cells and tumor cells at the 5% cut-off) and quantitative analyses (R(2) = 0.7991, 0.8187 for positive percentage and “H-score”). PD-L1 clone SP142 showed the highest positivity in immune/stromal cells staining (18.41%) compared to 28–8 (7.62%), while clone E1L3N showed poor staining in both tumor and immune/stromal cells. Clone SP142, but not 28–8 and E1L3N, predicted a worse prognosis at the 5% cut-off (p = 0.0243). Both the clone SP142 and 28–8 had high inter-pathologist correlation for tumor staining (R(2) = 0.9805 and R(2) = 0.9853), but a moderate correlation for stromal/immune cell staining (R(2) = 0.5653 and R(2) = 0.5745). Furthermore, a higher density of PD-L1(+)CD8(+) T cells was correlated with a shorter survival time (R(2) = 0.0909, p = 0.0352). CONCLUSIONS: PD-L1 antibody clone SP142 was superior in cell staining, particularly in immune/stromal cell and prognosis. These findings are important for selection of PD-L1 antibody clones in the future diagnostic test. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13000-018-0766-0) contains supplementary material, which is available to authorized users. BioMed Central 2018-11-21 /pmc/articles/PMC6249875/ /pubmed/30463584 http://dx.doi.org/10.1186/s13000-018-0766-0 Text en © The Author(s). 2018 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 Ma, Jing Li, Jianhui Qian, Meirui Han, Weili Tian, Miaomiao Li, Zengshan Wang, Zhe He, Shuixiang Wu, Kaichun PD-L1 expression and the prognostic significance in gastric cancer: a retrospective comparison of three PD-L1 antibody clones (SP142, 28–8 and E1L3N) |
title | PD-L1 expression and the prognostic significance in gastric cancer: a retrospective comparison of three PD-L1 antibody clones (SP142, 28–8 and E1L3N) |
title_full | PD-L1 expression and the prognostic significance in gastric cancer: a retrospective comparison of three PD-L1 antibody clones (SP142, 28–8 and E1L3N) |
title_fullStr | PD-L1 expression and the prognostic significance in gastric cancer: a retrospective comparison of three PD-L1 antibody clones (SP142, 28–8 and E1L3N) |
title_full_unstemmed | PD-L1 expression and the prognostic significance in gastric cancer: a retrospective comparison of three PD-L1 antibody clones (SP142, 28–8 and E1L3N) |
title_short | PD-L1 expression and the prognostic significance in gastric cancer: a retrospective comparison of three PD-L1 antibody clones (SP142, 28–8 and E1L3N) |
title_sort | pd-l1 expression and the prognostic significance in gastric cancer: a retrospective comparison of three pd-l1 antibody clones (sp142, 28–8 and e1l3n) |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6249875/ https://www.ncbi.nlm.nih.gov/pubmed/30463584 http://dx.doi.org/10.1186/s13000-018-0766-0 |
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