{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T00:59:09Z","timestamp":1760317149526,"version":"build-2065373602"},"reference-count":31,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2025,8,25]],"date-time":"2025-08-25T00:00:00Z","timestamp":1756080000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["pathsocjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pathology CR"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>PD\u2010L1 expression for the prediction of response to immune\u2010checkpoint 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\u2010L1 expression and heterogeneity in non\u2010small 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\u2010needle aspirates (FNAs) and two whole\u2010block tissue sections from each specimen. A matched biopsy, FNA, and whole\u2010block were placed into formalin or an alcohol\u2010based fixative (Cytolyt\u2122) prior to PD\u2010L1 immunohistochemistry assessment. A total of 114 specimens from 57 patients were included. All whole\u2010block cases (100%), 92% of core biopsies, and 88% of FNAs were adequate for PD\u2010L1 expression analysis. Fixation had no significant impact on adequacy, but cytology specimens fixed in alcohol showed a significant reduction in PD\u2010L1 expression, with 25% of cases placed into different clinically relevant categories of PD\u2010L1 expression. PD\u2010L1 expression by immunochemistry is an exemplar of the challenges of utilising a heterogeneously expressed protein\u2010based predictive biomarker. Regardless of sampling technique, a good quality biopsy or FNA is likely to give a statistically representative PD\u2010L1 expression, although expression ranges close to clinically relevant cut\u2010offs of 1% and 50% remain a source of potential discordance.<\/jats:p>","DOI":"10.1002\/2056-4538.70041","type":"journal-article","created":{"date-parts":[[2025,8,25]],"date-time":"2025-08-25T16:40:56Z","timestamp":1756140056000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Assessing <scp>PD<\/scp>\u2010<scp>L1<\/scp> expression in non\u2010small cell lung carcinoma: a prospective study of matched fine\u2010needle aspirates, core biopsies, and resection specimens using alcohol and forming fixatives"],"prefix":"10.1002","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9747-563X","authenticated-orcid":false,"given":"Alexander","family":"Haragan","sequence":"first","affiliation":[{"name":"Institute of Systems, Molecular and Integrative Biology University of Liverpool  Liverpool UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Natalie","family":"Kipling","sequence":"additional","affiliation":[{"name":"Institute of Systems, Molecular and Integrative Biology University of Liverpool  Liverpool UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Shackcloth","sequence":"additional","affiliation":[{"name":"Institute of Systems, Molecular and Integrative Biology University of Liverpool  Liverpool UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John R","family":"Gosney","sequence":"additional","affiliation":[{"name":"Institute of Systems, Molecular and Integrative Biology University of Liverpool  Liverpool UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael P","family":"Davies","sequence":"additional","affiliation":[{"name":"Institute of Systems, Molecular and Integrative Biology University of Liverpool  Liverpool UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John K","family":"Field","sequence":"additional","affiliation":[{"name":"Institute of Systems, Molecular and Integrative Biology University of Liverpool  Liverpool UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,8,25]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtho.2022.09.109"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mpdhp.2024.04.002"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2017.74.7642"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1504627"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1501824"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1507643"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtho.2018.04.039"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lungcan.2019.06.005"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncy.22216"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1136\/jcp-2022-208643"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1097\/JTO.0000000000000630"},{"key":"e_1_2_9_13_1","first-page":"138","volume-title":"International Union against Cancer (UICC): TNM Classification of Malignant Tumours","author":"Sobin L","year":"2011"},{"key":"e_1_2_9_14_1","unstructured":"Roche Ventana.VENTANA PD\u2010L1 (SP263) Assay.2017. 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