Heterogeneity of PD-L1 expression in non-small cell lung cancer: Implications for specimen sampling in predicting treatment response

Haragan, A ORCID: 0000-0002-9747-563X, Field, JK ORCID: 0000-0003-3951-6365, Davies, MPA ORCID: 0000-0002-7609-4977, Escriu, C ORCID: 0000-0003-3638-3202, Gruver, A and Gosney, JR (2019) Heterogeneity of PD-L1 expression in non-small cell lung cancer: Implications for specimen sampling in predicting treatment response. Lung Cancer, 134. pp. 79-84.

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Abstract

© 2019 The Authors Objectives: PD-L1 expression on tumour cells can guide the use of anti-PD-1/PD-L1 immune modulators to treat patients with non-small cell lung cancer (NSCLC). Heterogeneity of PD-L1 expression both within and between tumour sites is a well-documented phenomenon that compromises its predictive power. Our aim was to better characterise the pattern and extent of PD-L1 heterogeneity with a view to optimising tumour sampling and improve its accuracy as a biomarker. Materials and methods: Expression of PD-L1 was assessed by immunochemistry using the SP263 clone in 107 resected primary NSCLCs and their nodal metastases. Intra-tumoural heterogeneity, defined as ‘small-scale’ (mm²), ‘medium-scale’ (cm²) and ‘large-scale’ (between tumour blocks), was assessed by digital imaging using a novel ‘squares method’. Inter-tumoural heterogeneity between the primary tumours and their nodal metastases and between N1 and N2 nodal stages was also assessed. Results: The majority of tumours demonstrated intra-tumoural heterogeneity (small-scale 78%, medium-scale 50%, large-scale 46%). Inter-tumoural heterogeneity between the primary and nodal metastases was present in 53% of cases and, in 17%, between N1 and N2 disease. These differences were occasionally sufficient to lead to discrepancy across the ≥1%, ≥25% and ≥50% cut-offs used to guide therapy. Conclusion: Heterogeneity of PD-L1 expression is common, variable in scale and extent, and carries significant implications for its accuracy as a predictive biomarker. Extensive sampling reduces, but cannot eliminate, this inaccuracy.

Item Type:	Article
Uncontrolled Keywords:	PD-L1, Programmed-death ligand-1, NSCLC, Heterogeneity, Nodal metastases
Depositing User:	Symplectic Admin
Date Deposited:	23 Sep 2019 10:10
Last Modified:	19 Jan 2023 00:25
DOI:	10.1016/j.lungcan.2019.06.005
Open Access URL:	https://doi.org/10.1016/j.lungcan.2019.06.005
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3055620

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