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Intratumoural PD-L1 expression is associated with worse survival of patients with Epstein–Barr virus-associated gastric cancer

BACKGROUND: This study investigated the clinical relevance and prognostic impact of the overall expression of programmed cell death protein ligand-1 (PD-L1) and programmed cell death protein ligand-2 (PD-L2), in patients with Epstein–Barr virus-associated gastric cancer (EBVaGC). METHODS: After revi...

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Autores principales: Seo, An Na, Kang, Byung Woog, Kwon, Oh Kyoung, Park, Ki Bum, Lee, Seung Soo, Chung, Ho Young, Yu, Wansik, Bae, Han Ik, Jeon, Seong Woo, Kang, Hyojeung, Kim, Jong Gwang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5729479/
https://www.ncbi.nlm.nih.gov/pubmed/29073638
http://dx.doi.org/10.1038/bjc.2017.369
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author Seo, An Na
Kang, Byung Woog
Kwon, Oh Kyoung
Park, Ki Bum
Lee, Seung Soo
Chung, Ho Young
Yu, Wansik
Bae, Han Ik
Jeon, Seong Woo
Kang, Hyojeung
Kim, Jong Gwang
author_facet Seo, An Na
Kang, Byung Woog
Kwon, Oh Kyoung
Park, Ki Bum
Lee, Seung Soo
Chung, Ho Young
Yu, Wansik
Bae, Han Ik
Jeon, Seong Woo
Kang, Hyojeung
Kim, Jong Gwang
author_sort Seo, An Na
collection PubMed
description BACKGROUND: This study investigated the clinical relevance and prognostic impact of the overall expression of programmed cell death protein ligand-1 (PD-L1) and programmed cell death protein ligand-2 (PD-L2), in patients with Epstein–Barr virus-associated gastric cancer (EBVaGC). METHODS: After reviewing 1318 consecutive cases of surgically resected or endoscopic submucosal dissected gastric cancers, the expression status of PD-L1 and PD-L2 in 120 patients with EBVaGC identified by EBV-encoded RNA in situ hybridisation was retrospectively analysed using immunohistochemistry (IHC). For each IHC marker, positivity was separately in intraepithelial tumour cells (iTu-) and immune cells in the tumour stroma area (str-). RESULTS: Among 116 eligible patients, 57 (49.1%) and 66 patients (56.9%) were determined as iTu-PD-L1-positive and str-PD-L1-positive, respectively, whereas 23 (21.6%) and 45 patients (38.8%) were determined as iTu-PD-L2 positive and str-PD-L2 positive, respectively. Intraepithelial tumour cell PD-L1 positivity was found to be significantly associated with lymph node (LN) metastasis (P=0.012) and a poor disease-free survival (DFS) (P=0.032), yet not overall survival (P=0.482). In a multivariate analysis, iTu-PD-L1 positivity was independently associated with a poor DFS (P=0.006, hazard ratio=12.085). In contrast, str-PD-L2-positivity was related to a lower T category (P=0.003), absence of LN metastasis (P=0.032) and perineural invasion (P=0.028). Intraepithelial tumour cell and str-PD-L2 positivity showed a trend towards an improved DFS, although not significant (P=0.060 and P=0.073, respectively). CONCLUSIONS: Intraepithelial tumour cells PD-L1 expression can be used to predict a poor outcome in patients with EBVaGC and can represent a rational approach for PD-1/PD-L pathway-targeted immunotherapy.
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spelling pubmed-57294792018-12-05 Intratumoural PD-L1 expression is associated with worse survival of patients with Epstein–Barr virus-associated gastric cancer Seo, An Na Kang, Byung Woog Kwon, Oh Kyoung Park, Ki Bum Lee, Seung Soo Chung, Ho Young Yu, Wansik Bae, Han Ik Jeon, Seong Woo Kang, Hyojeung Kim, Jong Gwang Br J Cancer Clinical Study BACKGROUND: This study investigated the clinical relevance and prognostic impact of the overall expression of programmed cell death protein ligand-1 (PD-L1) and programmed cell death protein ligand-2 (PD-L2), in patients with Epstein–Barr virus-associated gastric cancer (EBVaGC). METHODS: After reviewing 1318 consecutive cases of surgically resected or endoscopic submucosal dissected gastric cancers, the expression status of PD-L1 and PD-L2 in 120 patients with EBVaGC identified by EBV-encoded RNA in situ hybridisation was retrospectively analysed using immunohistochemistry (IHC). For each IHC marker, positivity was separately in intraepithelial tumour cells (iTu-) and immune cells in the tumour stroma area (str-). RESULTS: Among 116 eligible patients, 57 (49.1%) and 66 patients (56.9%) were determined as iTu-PD-L1-positive and str-PD-L1-positive, respectively, whereas 23 (21.6%) and 45 patients (38.8%) were determined as iTu-PD-L2 positive and str-PD-L2 positive, respectively. Intraepithelial tumour cell PD-L1 positivity was found to be significantly associated with lymph node (LN) metastasis (P=0.012) and a poor disease-free survival (DFS) (P=0.032), yet not overall survival (P=0.482). In a multivariate analysis, iTu-PD-L1 positivity was independently associated with a poor DFS (P=0.006, hazard ratio=12.085). In contrast, str-PD-L2-positivity was related to a lower T category (P=0.003), absence of LN metastasis (P=0.032) and perineural invasion (P=0.028). Intraepithelial tumour cell and str-PD-L2 positivity showed a trend towards an improved DFS, although not significant (P=0.060 and P=0.073, respectively). CONCLUSIONS: Intraepithelial tumour cells PD-L1 expression can be used to predict a poor outcome in patients with EBVaGC and can represent a rational approach for PD-1/PD-L pathway-targeted immunotherapy. Nature Publishing Group 2017-12-05 2017-10-26 /pmc/articles/PMC5729479/ /pubmed/29073638 http://dx.doi.org/10.1038/bjc.2017.369 Text en Copyright © 2017 Cancer Research UK http://creativecommons.org/licenses/by-nc-sa/4.0/ From twelve months after its original publication, this work is licensed under the Creative Commons Attribution-NonCommercial-Share Alike 4.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/4.0/
spellingShingle Clinical Study
Seo, An Na
Kang, Byung Woog
Kwon, Oh Kyoung
Park, Ki Bum
Lee, Seung Soo
Chung, Ho Young
Yu, Wansik
Bae, Han Ik
Jeon, Seong Woo
Kang, Hyojeung
Kim, Jong Gwang
Intratumoural PD-L1 expression is associated with worse survival of patients with Epstein–Barr virus-associated gastric cancer
title Intratumoural PD-L1 expression is associated with worse survival of patients with Epstein–Barr virus-associated gastric cancer
title_full Intratumoural PD-L1 expression is associated with worse survival of patients with Epstein–Barr virus-associated gastric cancer
title_fullStr Intratumoural PD-L1 expression is associated with worse survival of patients with Epstein–Barr virus-associated gastric cancer
title_full_unstemmed Intratumoural PD-L1 expression is associated with worse survival of patients with Epstein–Barr virus-associated gastric cancer
title_short Intratumoural PD-L1 expression is associated with worse survival of patients with Epstein–Barr virus-associated gastric cancer
title_sort intratumoural pd-l1 expression is associated with worse survival of patients with epstein–barr virus-associated gastric cancer
topic Clinical Study
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5729479/
https://www.ncbi.nlm.nih.gov/pubmed/29073638
http://dx.doi.org/10.1038/bjc.2017.369
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