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Intratumoral heterogeneity of programmed cell death ligand-1 expression is common in lung cancer

Programmed cell death ligand-1 (PD-L1) expression may predict the response to both programmed cell death-1 and PD-L1 inhibitors in lung cancer. However, the extent of intratumoral heterogeneity of PD-L1 expression, which may cause false negative results, is largely unexplored. We aimed to assess the...

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Autores principales: Nakamura, Sayuri, Hayashi, Kentaro, Imaoka, Yuki, Kitamura, Yuka, Akazawa, Yuko, Tabata, Kazuhiro, Groen, Ruben, Tsuchiya, Tomoshi, Yamasaki, Naoya, Nagayasu, Takeshi, Fukuoka, Junya
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5648155/
https://www.ncbi.nlm.nih.gov/pubmed/29049375
http://dx.doi.org/10.1371/journal.pone.0186192
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author Nakamura, Sayuri
Hayashi, Kentaro
Imaoka, Yuki
Kitamura, Yuka
Akazawa, Yuko
Tabata, Kazuhiro
Groen, Ruben
Tsuchiya, Tomoshi
Yamasaki, Naoya
Nagayasu, Takeshi
Fukuoka, Junya
author_facet Nakamura, Sayuri
Hayashi, Kentaro
Imaoka, Yuki
Kitamura, Yuka
Akazawa, Yuko
Tabata, Kazuhiro
Groen, Ruben
Tsuchiya, Tomoshi
Yamasaki, Naoya
Nagayasu, Takeshi
Fukuoka, Junya
author_sort Nakamura, Sayuri
collection PubMed
description Programmed cell death ligand-1 (PD-L1) expression may predict the response to both programmed cell death-1 and PD-L1 inhibitors in lung cancer. However, the extent of intratumoral heterogeneity of PD-L1 expression, which may cause false negative results, is largely unexplored. We aimed to assess the intratumoral heterogeneity of PD-L1 expression in surgically resected lung cancer specimens by applying a novel method of tissue microarray, namely Spiral Arrays, which enables us to observe the heterogeneity in spiral-shaped tissue cores. Adenocarcinoma and squamous cell carcinoma specimens were obtained from consecutive patients with lung cancer who had undergone surgical resection at Nagasaki University Hospital (Nagasaki, Japan) since 2009. Small cell lung cancer and large cell carcinoma specimens were selected from patients in the same archive who had undergone resection since 1998. Spiral Arrays were constructed of spiral-shaped cores, prepared from representative blocks of each case, which were subjected to immunohistochemistry using an anti-PD-L1 antibody. Each core was divided into 8 segments and each segment was classified as either PD-L1-positive or PD-L1-negative using thresholds of 1.0%, 5.0%, 10.0%, and 50.0%, respectively. In total, 138 specimens were selected, including 60 adenocarcinomas, 59 squamous cell carcinomas, 12 small cell lung cancers, and 7 large cell carcinomas. The majority of specimens with PD-L1-positive segments exhibited heterogeneous expression (i.e., had a mixture of PD-L1-positive and PD-L1-negative segments within a core) irrespective of the threshold (1.0%, 66.7%; 5.0%, 74.4%; 10.0%, 75.8%; and 50.0%, 85.7%]. Large variations in the ratios of PD-L1-positive segments were observed. At least 50.0% of the segments within a core were negative in no fewer than 50.0% (range, 50.0–76.0%) of cases with heterogeneous PD-L1 expression. In conclusion, intratumoral heterogeneity of PD-L1 expression was frequently observed in cases of lung cancer. Thus, multiple tumor biopsy specimens may be needed to accurately determine the PD-L1 expression status.
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spelling pubmed-56481552017-11-03 Intratumoral heterogeneity of programmed cell death ligand-1 expression is common in lung cancer Nakamura, Sayuri Hayashi, Kentaro Imaoka, Yuki Kitamura, Yuka Akazawa, Yuko Tabata, Kazuhiro Groen, Ruben Tsuchiya, Tomoshi Yamasaki, Naoya Nagayasu, Takeshi Fukuoka, Junya PLoS One Research Article Programmed cell death ligand-1 (PD-L1) expression may predict the response to both programmed cell death-1 and PD-L1 inhibitors in lung cancer. However, the extent of intratumoral heterogeneity of PD-L1 expression, which may cause false negative results, is largely unexplored. We aimed to assess the intratumoral heterogeneity of PD-L1 expression in surgically resected lung cancer specimens by applying a novel method of tissue microarray, namely Spiral Arrays, which enables us to observe the heterogeneity in spiral-shaped tissue cores. Adenocarcinoma and squamous cell carcinoma specimens were obtained from consecutive patients with lung cancer who had undergone surgical resection at Nagasaki University Hospital (Nagasaki, Japan) since 2009. Small cell lung cancer and large cell carcinoma specimens were selected from patients in the same archive who had undergone resection since 1998. Spiral Arrays were constructed of spiral-shaped cores, prepared from representative blocks of each case, which were subjected to immunohistochemistry using an anti-PD-L1 antibody. Each core was divided into 8 segments and each segment was classified as either PD-L1-positive or PD-L1-negative using thresholds of 1.0%, 5.0%, 10.0%, and 50.0%, respectively. In total, 138 specimens were selected, including 60 adenocarcinomas, 59 squamous cell carcinomas, 12 small cell lung cancers, and 7 large cell carcinomas. The majority of specimens with PD-L1-positive segments exhibited heterogeneous expression (i.e., had a mixture of PD-L1-positive and PD-L1-negative segments within a core) irrespective of the threshold (1.0%, 66.7%; 5.0%, 74.4%; 10.0%, 75.8%; and 50.0%, 85.7%]. Large variations in the ratios of PD-L1-positive segments were observed. At least 50.0% of the segments within a core were negative in no fewer than 50.0% (range, 50.0–76.0%) of cases with heterogeneous PD-L1 expression. In conclusion, intratumoral heterogeneity of PD-L1 expression was frequently observed in cases of lung cancer. Thus, multiple tumor biopsy specimens may be needed to accurately determine the PD-L1 expression status. Public Library of Science 2017-10-19 /pmc/articles/PMC5648155/ /pubmed/29049375 http://dx.doi.org/10.1371/journal.pone.0186192 Text en © 2017 Nakamura et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Nakamura, Sayuri
Hayashi, Kentaro
Imaoka, Yuki
Kitamura, Yuka
Akazawa, Yuko
Tabata, Kazuhiro
Groen, Ruben
Tsuchiya, Tomoshi
Yamasaki, Naoya
Nagayasu, Takeshi
Fukuoka, Junya
Intratumoral heterogeneity of programmed cell death ligand-1 expression is common in lung cancer
title Intratumoral heterogeneity of programmed cell death ligand-1 expression is common in lung cancer
title_full Intratumoral heterogeneity of programmed cell death ligand-1 expression is common in lung cancer
title_fullStr Intratumoral heterogeneity of programmed cell death ligand-1 expression is common in lung cancer
title_full_unstemmed Intratumoral heterogeneity of programmed cell death ligand-1 expression is common in lung cancer
title_short Intratumoral heterogeneity of programmed cell death ligand-1 expression is common in lung cancer
title_sort intratumoral heterogeneity of programmed cell death ligand-1 expression is common in lung cancer
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5648155/
https://www.ncbi.nlm.nih.gov/pubmed/29049375
http://dx.doi.org/10.1371/journal.pone.0186192
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