Haragan, A 
ORCID: 0000-0002-9747-563X, Kipling, N, Shackcloth, M, Gosney, JR, Davies, MP ORCID: 0000-0002-7609-4977 and Field, JK ORCID: 0000-0003-3951-6365
(2025)
Assessing PD-L1 expression in non-small cell lung carcinoma: a prospective study of matched fine-needle aspirates, core biopsies, and resection specimens using alcohol and forming fixatives
Journal of Pathology Clinical Research, 11 (5).
e70041-.
ISSN 2056-4538, 2056-4538
Abstract
PD-L1 expression for the prediction of response to immune-checkpoint blockade remains the most broadly utilised clinically validated biomarker in a range of tumour types. In this study, we aimed to assess, in a prospectively collected matched cohort, the impact of sampling technique and both formalin and alcohol fixation on PD-L1 expression and heterogeneity in non-small cell lung carcinoma (NSCLC). Patients undergoing surgical resection for NSCLC were consented. Surgical specimens were received directly from theatre and sampled fresh to produce two sets of core biopsies, two fine-needle aspirates (FNAs) and two whole-block tissue sections from each specimen. A matched biopsy, FNA, and whole-block were placed into formalin or an alcohol-based fixative (Cytolyt™) prior to PD-L1 immunohistochemistry assessment. A total of 114 specimens from 57 patients were included. All whole-block cases (100%), 92% of core biopsies, and 88% of FNAs were adequate for PD-L1 expression analysis. Fixation had no significant impact on adequacy, but cytology specimens fixed in alcohol showed a significant reduction in PD-L1 expression, with 25% of cases placed into different clinically relevant categories of PD-L1 expression. PD-L1 expression by immunochemistry is an exemplar of the challenges of utilising a heterogeneously expressed protein-based predictive biomarker. Regardless of sampling technique, a good quality biopsy or FNA is likely to give a statistically representative PD-L1 expression, although expression ranges close to clinically relevant cut-offs of 1% and 50% remain a source of potential discordance.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | assay, digital microscopy, immunocytochemistry, lung |
| Divisions: | Faculty of Health & Life Sciences Faculty of Health & Life Sciences > Inst. Systems, Molec & Integrative Biology > Inst. Systems, Molec & Integrative Biology |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 01 Sep 2025 15:31 |
| Last Modified: | 28 Feb 2026 15:59 |
| DOI: | 10.1002/2056-4538.70041 |
| Open Access URL: | https://pathsocjournals.onlinelibrary.wiley.com/do... |
| Related Websites: | |
| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3194245 |
| Disclaimer: | The University of Liverpool is not responsible for content contained on other websites from links within repository metadata. Please contact us if you notice anything that appears incorrect or inappropriate. |
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