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PD-L1 expression in non-small cell lung cancer: heterogeneity by pathologic types, tissue sampling and metastasis

BACKGROUND: Programmed cell death ligand-1 (PD-L1) is a predictive marker of anti-PD-1/PD-L1 therapy response. Intra-tumour heterogeneity of PD-L1 expression has been reported in non-small cell lung cancer (NSCLC), but comprehensive studies regarding the determination of PD-L1 expression in differen...

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Autores principales: Shen, Xuxia, Wang, Yue, Jin, Yan, Zheng, Qiang, Shen, Lei, Chen, Ying, Li, Yuan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: AME Publishing Company 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8339751/
https://www.ncbi.nlm.nih.gov/pubmed/34422362
http://dx.doi.org/10.21037/jtd-21-388
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author Shen, Xuxia
Wang, Yue
Jin, Yan
Zheng, Qiang
Shen, Lei
Chen, Ying
Li, Yuan
author_facet Shen, Xuxia
Wang, Yue
Jin, Yan
Zheng, Qiang
Shen, Lei
Chen, Ying
Li, Yuan
author_sort Shen, Xuxia
collection PubMed
description BACKGROUND: Programmed cell death ligand-1 (PD-L1) is a predictive marker of anti-PD-1/PD-L1 therapy response. Intra-tumour heterogeneity of PD-L1 expression has been reported in non-small cell lung cancer (NSCLC), but comprehensive studies regarding the determination of PD-L1 expression in different materials are still lacking. Therefore, we aimed to compare PD-L1 expression in paired tumour samples and in different specimen types. METHODS: A total of 1,002 resected NSCLC specimens, 35 biopsy specimens and 54 endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) samples were performed PD-L1 immunohistochemistry (IHC) testing using the 22C3 assay. PD-L1 expression was evaluated using the tumour proportion score (TPS) and categorized into three levels: negative (TPS <1%), low expression (TPS 1–49%) and high expression (TPS ≥50%). RESULTS: A total of 1,002 resected NSCLC specimens, including 852 adenocarcinomas (ADCs) and 150 squamous cell carcinomas (SCCs); 35 paired biopsy and resected samples; 54 paired cell block and biopsy samples; 53 paired blocks from the same resected tissue and 49 paired primary and metastatic lesion samples were included in this study. Interestingly, high PD-L1 expression was significantly more frequent in poorly differentiated subtypes than in well-differentiated subtypes in the ADC subgroup (P<0.001). In the SCC subgroup, high PD-L1 expression was significantly more associated with the nonkeratinizing type than the keratinizing type (P=0.001). PD-L1 expression differed between cell blocks and matched biopsy specimens (discordance rate =11.1%, 6/54) and between biopsy and matched resected specimens (discordance rate =31.4%, 11/35). PD-L1 expression differed between different paraffin blocks from the same resected specimen (discordance rate =35.8%, 19/53), and the discordance rate of PD-L1 expression between primary tumours and matched lymph node metastases was 28.6% (14/49). CONCLUSIONS: Discordant PD-L1 expression is not uncommon in NSCLC and warrants additional studies and serious consideration when interpreting PD-L1 test results. Initial negative test results may lead to repeat PD-L1 testing in additional samples or the use of a different clone if necessary.
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spelling pubmed-83397512021-08-20 PD-L1 expression in non-small cell lung cancer: heterogeneity by pathologic types, tissue sampling and metastasis Shen, Xuxia Wang, Yue Jin, Yan Zheng, Qiang Shen, Lei Chen, Ying Li, Yuan J Thorac Dis Original Article BACKGROUND: Programmed cell death ligand-1 (PD-L1) is a predictive marker of anti-PD-1/PD-L1 therapy response. Intra-tumour heterogeneity of PD-L1 expression has been reported in non-small cell lung cancer (NSCLC), but comprehensive studies regarding the determination of PD-L1 expression in different materials are still lacking. Therefore, we aimed to compare PD-L1 expression in paired tumour samples and in different specimen types. METHODS: A total of 1,002 resected NSCLC specimens, 35 biopsy specimens and 54 endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) samples were performed PD-L1 immunohistochemistry (IHC) testing using the 22C3 assay. PD-L1 expression was evaluated using the tumour proportion score (TPS) and categorized into three levels: negative (TPS <1%), low expression (TPS 1–49%) and high expression (TPS ≥50%). RESULTS: A total of 1,002 resected NSCLC specimens, including 852 adenocarcinomas (ADCs) and 150 squamous cell carcinomas (SCCs); 35 paired biopsy and resected samples; 54 paired cell block and biopsy samples; 53 paired blocks from the same resected tissue and 49 paired primary and metastatic lesion samples were included in this study. Interestingly, high PD-L1 expression was significantly more frequent in poorly differentiated subtypes than in well-differentiated subtypes in the ADC subgroup (P<0.001). In the SCC subgroup, high PD-L1 expression was significantly more associated with the nonkeratinizing type than the keratinizing type (P=0.001). PD-L1 expression differed between cell blocks and matched biopsy specimens (discordance rate =11.1%, 6/54) and between biopsy and matched resected specimens (discordance rate =31.4%, 11/35). PD-L1 expression differed between different paraffin blocks from the same resected specimen (discordance rate =35.8%, 19/53), and the discordance rate of PD-L1 expression between primary tumours and matched lymph node metastases was 28.6% (14/49). CONCLUSIONS: Discordant PD-L1 expression is not uncommon in NSCLC and warrants additional studies and serious consideration when interpreting PD-L1 test results. Initial negative test results may lead to repeat PD-L1 testing in additional samples or the use of a different clone if necessary. AME Publishing Company 2021-07 /pmc/articles/PMC8339751/ /pubmed/34422362 http://dx.doi.org/10.21037/jtd-21-388 Text en 2021 Journal of Thoracic Disease. All rights reserved. https://creativecommons.org/licenses/by-nc-nd/4.0/Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0 (https://creativecommons.org/licenses/by-nc-nd/4.0/) .
spellingShingle Original Article
Shen, Xuxia
Wang, Yue
Jin, Yan
Zheng, Qiang
Shen, Lei
Chen, Ying
Li, Yuan
PD-L1 expression in non-small cell lung cancer: heterogeneity by pathologic types, tissue sampling and metastasis
title PD-L1 expression in non-small cell lung cancer: heterogeneity by pathologic types, tissue sampling and metastasis
title_full PD-L1 expression in non-small cell lung cancer: heterogeneity by pathologic types, tissue sampling and metastasis
title_fullStr PD-L1 expression in non-small cell lung cancer: heterogeneity by pathologic types, tissue sampling and metastasis
title_full_unstemmed PD-L1 expression in non-small cell lung cancer: heterogeneity by pathologic types, tissue sampling and metastasis
title_short PD-L1 expression in non-small cell lung cancer: heterogeneity by pathologic types, tissue sampling and metastasis
title_sort pd-l1 expression in non-small cell lung cancer: heterogeneity by pathologic types, tissue sampling and metastasis
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8339751/
https://www.ncbi.nlm.nih.gov/pubmed/34422362
http://dx.doi.org/10.21037/jtd-21-388
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