{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T15:22:59Z","timestamp":1786980179332,"version":"build-2736575974"},"reference-count":44,"publisher":"Springer Science and Business Media LLC","issue":"5","license":[{"start":{"date-parts":[[2020,12,4]],"date-time":"2020-12-04T00:00:00Z","timestamp":1607040000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2020,12,4]],"date-time":"2020-12-04T00:00:00Z","timestamp":1607040000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Pfizer Oncology","award":["not applicable"],"award-info":[{"award-number":["not applicable"]}]},{"DOI":"10.13039\/100002491","name":"Bristol-Myers Squibb","doi-asserted-by":"publisher","award":["not applicable"],"award-info":[{"award-number":["not applicable"]}],"id":[{"id":"10.13039\/100002491","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Virchows Arch"],"published-print":{"date-parts":[[2021,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Programmed death ligand 1 (PD-L1) immunohistochemistry (IHC) is accepted as a predictive biomarker for the selection of immune checkpoint inhibitors. We evaluated the staining quality and estimation of the tumor proportion score (TPS) in non-small-cell lung cancer during two external quality assessment (EQA) schemes by the European Society of Pathology. Participants received two tissue micro-arrays with three (2017) and four (2018) cases for PD-L1 IHC and a positive tonsil control, for staining by their routine protocol. After the participants returned stained slides to the EQA coordination center, three pathologists assessed each slide and awarded an expert staining score from 1 to 5 points based on the staining concordance. Expert scores significantly (\n                    <jats:italic>p<\/jats:italic>\n                    &lt; 0.01) improved between EQA schemes from 3.8 (\n                    <jats:italic>n<\/jats:italic>\n                    = 67) to 4.3 (\n                    <jats:italic>n<\/jats:italic>\n                    = 74) on 5 points. Participants used 32 different protocols: the majority applied the 22C3 (56.7%) (Dako), SP263 (19.1%) (Ventana), and E1L3N (Cell Signaling) (7.1%) clones. Staining artifacts consisted mainly of very weak or weak antigen demonstration (63.0%) or excessive background staining (19.8%). Participants using CE-IVD kits reached a higher score compared with those using laboratory-developed tests (LDTs) (\n                    <jats:italic>p<\/jats:italic>\n                    &lt; 0.05), mainly attributed to a better concordance of SP263. The TPS was under- and over-estimated in 20\/423 (4.7%) and 24\/423 (5.7%) cases, respectively, correlating to a lower expert score. Additional research is needed on the concordance of less common protocols, and on reasons for lower LDT concordance. Laboratories should carefully validate all test methods and regularly verify their performance. EQA participation should focus on both staining concordance and interpretation of PD-L1 IHC.\n                  <\/jats:p>","DOI":"10.1007\/s00428-020-02976-5","type":"journal-article","created":{"date-parts":[[2020,12,4]],"date-time":"2020-12-04T04:05:52Z","timestamp":1607054752000},"page":"827-839","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["PD-L1 immunohistochemistry in non-small-cell lung cancer: unraveling differences in staining concordance and interpretation"],"prefix":"10.1007","volume":"478","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4498-8386","authenticated-orcid":false,"given":"Cleo","family":"Keppens","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabeth MC","family":"Dequeker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8553-1921","authenticated-orcid":false,"given":"Patrick","family":"Pauwels","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3051-2280","authenticated-orcid":false,"given":"Ales","family":"Ryska","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nils","family":"\u2018t Hart","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9699-4860","authenticated-orcid":false,"given":"Jan H","family":"von der Th\u00fcsen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,12,4]]},"reference":[{"key":"2976_CR1","unstructured":"Food and Drug Administration (2019) Nivolumab prescribing information. https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2019\/125554s070lbl.pdf. Accessed 30 Mar 2020"},{"key":"2976_CR2","unstructured":"European Medicines Agency (2019) Opdivo European public assessment report. https:\/\/www.ema.europa.eu\/en\/documents\/overview\/opdivo-epar-medicine-overview_en.pdf. Accessed 30 Mar 2020"},{"key":"2976_CR3","unstructured":"Food and Drug Administration (2020) Pembrolizumab prescribing information. https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2020\/125514s066lbl.pdf. Accessed 30 Mar 2020"},{"key":"2976_CR4","unstructured":"European Medicines Agency (2019) Keytruda European public assessment report. https:\/\/www.ema.europa.eu\/en\/documents\/overview\/keytruda-epar-medicine-overview_en.pdf. Accessed 30 Mar 2020"},{"key":"2976_CR5","unstructured":"Food and Drug Administration (2019) Atezolizumab prescribing information. https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2019\/761034s018lbl.pdf. Accessed 30 Mar 2020"},{"key":"2976_CR6","unstructured":"European Medicines Agency (2019) Tecentriq European public assessment report. https:\/\/www.ema.europa.eu\/en\/documents\/overview\/tecentriq-epar-medicine-overview_en.pdf. Accessed 30 Mar 2020"},{"key":"2976_CR7","doi-asserted-by":"publisher","unstructured":"Ellis PM, Vella ET, Ung YC (2017) Immune checkpoint inhibitors for patients with advanced non-small-cell lung cancer: a systematic review. Clin Lung Cancer 18(5):444\u2013459.e1. https:\/\/doi.org\/10.1016\/j.cllc.2017.02.001","DOI":"10.1016\/j.cllc.2017.02.001"},{"key":"2976_CR8","doi-asserted-by":"publisher","first-page":"7369","DOI":"10.2147\/OTT.S177318","volume":"11","author":"M Peng","year":"2018","unstructured":"Peng M, Li X, Lei G, Weng YM, Hu MX, Song QB (2018) The efficacy and safety of immune checkpoint inhibitor combination therapy in lung cancer: a systematic review and meta-analysis. Onco Targets Ther 11:7369\u20137383. https:\/\/doi.org\/10.2147\/OTT.S177318","journal-title":"Onco Targets Ther"},{"key":"2976_CR9","unstructured":"Food and Drug Administration (2020) https:\/\/www.accessdata.fda.gov. Accessed 30 Mar 2020"},{"key":"2976_CR10","unstructured":"European Medicines Agency (2020) https:\/\/www.ema.europa.eu. Accessed 30 Mar 2020"},{"key":"2976_CR11","unstructured":"Food and Drug Administration, Durvalumab prescribing information (2018) https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2018\/761069s002lbl.pdf. Accessed 30 Mar 2020"},{"key":"2976_CR12","unstructured":"European Medicines Agency (2018) Imfinzi public assessment report. https:\/\/www.ema.europa.eu\/en\/documents\/overview\/imfizi-epar-medicine-overview_en.pdf. Accessed 30 Mar 2020"},{"key":"2976_CR13","unstructured":"European Counsil Directive (2004) The European Parliament and of the Council of 31 March 2004 on setting standards of quality and safety for the donation, procurement, testing, processing, preservation, storage and distribution of human tissues and cells. 2004\/23\/EC."},{"key":"2976_CR14","unstructured":"Food and Drug Administration (2020) List of cleared or approved companion diagnostic devices (in vitro and imaging tools). https:\/\/www.fda.gov\/medical-devices\/vitro-diagnostics\/list-cleared-or-approved-companion-diagnostic-devices-vitro-and-imaging-tools. Accessed 30 March 2020"},{"key":"2976_CR15","doi-asserted-by":"publisher","first-page":"175883591876349","DOI":"10.1177\/1758835918763493","volume":"10","author":"C Teixid\u00f3","year":"2018","unstructured":"Teixid\u00f3 C, Vilari\u00f1o N, Reyes R, Reguart N (2018) PD-L1 expression testing in non-small cell lung cancer. Ther Adv Med Oncol 10:1758835918763493. https:\/\/doi.org\/10.1177\/1758835918763493","journal-title":"Ther Adv Med Oncol"},{"issue":"10","key":"2976_CR16","doi-asserted-by":"publisher","first-page":"1165","DOI":"10.1038\/modpathol.2016.117","volume":"29","author":"AH Scheel","year":"2016","unstructured":"Scheel AH, Dietel M, Heukamp LC, J\u00f6hrens K, Kirchner T, Reu S, R\u00fcschoff J, Schildhaus HU, Schirmacher P, Tiemann M, Warth A, Weichert W, Fischer RN, Wolf J, Buettner R (2016) Harmonized PD-L1 immunohistochemistry for pulmonary squamous-cell and adenocarcinomas. Mod Pathol 29(10):1165\u20131172. https:\/\/doi.org\/10.1038\/modpathol.2016.117","journal-title":"Mod Pathol"},{"issue":"34","key":"2976_CR17","doi-asserted-by":"publisher","first-page":"3867","DOI":"10.1200\/JCO.2017.74.7642","volume":"35","author":"R B\u00fcttner","year":"2017","unstructured":"B\u00fcttner R, Gosney JR, Skov BG, Adam J, Motoi N, Bloom KJ, Dietel M, Longshore JW, L\u00f3pez-R\u00edos F, Penault-Llorca F, Viale G, Wotherspoon AC, Kerr KM, Tsao MS (2017) Programmed death-ligand 1 immunohistochemistry testing: a review of analytical assays and clinical implementation in non-small-cell lung cancer. J Clin Oncol 35(34):3867\u20133876. https:\/\/doi.org\/10.1200\/JCO.2017.74.7642","journal-title":"J Clin Oncol"},{"issue":"2","key":"2976_CR18","doi-asserted-by":"publisher","first-page":"208","DOI":"10.1016\/j.jtho.2016.11.2228","volume":"12","author":"FR Hirsch","year":"2017","unstructured":"Hirsch FR, McElhinny A, Stanforth D, Ranger-Moore J, Jansson M, Kulangara K, Richardson W, Towne P, Hanks D, Vennapusa B, Mistry A, Kalamegham R, Averbuch S, Novotny J, Rubin E, Emancipator K, McCaffery I, Williams JA, Walker J, Longshore J, Tsao MS, Kerr KM (2017) PD-L1 immunohistochemistry assays for lung cancer: results from phase 1 of the blueprint PD-L1 IHC assay comparison project. J Thorac Oncol 12(2):208\u2013222. https:\/\/doi.org\/10.1016\/j.jtho.2016.11.2228","journal-title":"J Thorac Oncol"},{"issue":"14","key":"2976_CR19","doi-asserted-by":"publisher","first-page":"3585","DOI":"10.1158\/1078-0432.CCR-16-2375","volume":"23","author":"MJ Ratcliffe","year":"2017","unstructured":"Ratcliffe MJ, Sharpe A, Midha A, Barker C, Scott M, Scorer P, Al-Masri H, Rebelatto MC, Walker J (2017) Agreement between programmed cell death ligand-1 diagnostic assays across multiple protein expression cutoffs in non-small cell lung cancer. Clin Cancer Res 23(14):3585\u20133591. https:\/\/doi.org\/10.1158\/1078-0432.CCR-16-2375","journal-title":"Clin Cancer Res"},{"issue":"8","key":"2976_CR20","doi-asserted-by":"publisher","first-page":"1051","DOI":"10.1001\/jamaoncol.2017.0013","volume":"3","author":"DL Rimm","year":"2017","unstructured":"Rimm DL, Han G, Taube JM, Yi ES, Bridge JA, Flieder DB, Homer R, West WW, Wu H, Roden AC, Fujimoto J, Yu H, Anders R, Kowalewski A, Rivard C, Rehman J, Batenchuk C, Burns V, Hirsch FR, Wistuba II (2017) A prospective, multi-institutional, pathologist-based assessment of 4 immunohistochemistry assays for PD-L1 expression in non-small cell lung cancer. JAMA Oncol 3(8):1051\u20131058. https:\/\/doi.org\/10.1001\/jamaoncol.2017.0013","journal-title":"JAMA Oncol"},{"issue":"4","key":"2976_CR21","doi-asserted-by":"publisher","first-page":"953","DOI":"10.1093\/annonc\/mdy014","volume":"29","author":"J Adam","year":"2018","unstructured":"Adam J, Le Stang N, Rouquette I, Cazes A, Badoual C, Pinot-Roussel H, Tixier L, Danel C, Damiola F, Damotte D, Penault-Llorca F, Lantu\u00e9joul S (2018) Multicenter harmonization study for PD-L1 IHC testing in non-small-cell lung cancer. Ann Oncol 29(4):953\u2013958. https:\/\/doi.org\/10.1093\/annonc\/mdy014","journal-title":"Ann Oncol"},{"issue":"9","key":"2976_CR22","doi-asserted-by":"publisher","first-page":"1302","DOI":"10.1016\/j.jtho.2018.05.013","volume":"13","author":"MS Tsao","year":"2018","unstructured":"Tsao MS, Kerr KM, Kockx M, Beasley MB, Borczuk AC, Botling J, Bubendorf L, Chirieac L, Chen G, Chou TY, Chung JH, Dacic S, Lantuejoul S, Mino-Kenudson M, Moreira AL, Nicholson AG, Noguchi M, Pelosi G, Poleri C, Russell PA, Sauter J, Thunnissen E, Wistuba I, Yu H, Wynes MW, Pintilie M, Yatabe Y, Hirsch FR (2018) PD-L1 immunohistochemistry comparability study in real-life clinical samples: results of blueprint phase 2 project. J Thorac Oncol 13(9):1302\u20131311. https:\/\/doi.org\/10.1016\/j.jtho.2018.05.013","journal-title":"J Thorac Oncol"},{"key":"2976_CR23","doi-asserted-by":"crossref","unstructured":"Lantuejoul S, Damotte D, Hofman V, Adam J (2019) Programmed death ligand 1 immunohistochemistry in non-small cell lung carcinoma. J Thorac Dis 11(Suppl 1):S89\u2013S101. 10.21037\/jtd.2018.12.103","DOI":"10.21037\/jtd.2018.12.103"},{"issue":"3","key":"2976_CR24","doi-asserted-by":"publisher","first-page":"321","DOI":"10.5858\/arpa.2017-0388-CP","volume":"142","author":"NI Lindeman","year":"2018","unstructured":"Lindeman NI, Cagle PT, Aisner DL, Arcila ME, Beasley MB, Bernicker EH, Colasacco C, Dacic S, Hirsch FR, Kerr K, Kwiatkowski DJ, Ladanyi M, Nowak JA, Sholl L, Temple-Smolkin R, Solomon B, Souter LH, Thunnissen E, Tsao MS, Ventura CB, Wynes MW, Yatabe Y (2018) Updated molecular testing guideline for the selection of lung cancer patients for treatment with targeted tyrosine kinase inhibitors: guideline from the College of American Pathologists, the International Association for the Study of Lung Cancer, and the Association for Molecular Pathology. Arch Pathol Lab Med 142(3):321\u2013346. https:\/\/doi.org\/10.5858\/arpa.2017-0388-CP","journal-title":"Arch Pathol Lab Med"},{"issue":"9","key":"2976_CR25","doi-asserted-by":"publisher","first-page":"1247","DOI":"10.5858\/arpa.2016-0558-CP","volume":"141","author":"PL Fitzgibbons","year":"2017","unstructured":"Fitzgibbons PL, Goldsmith JD, Souers RJ, Fatheree LA, Volmar KE, Stuart LN, Nowak JA, Astles JR, Nakhleh RE (2017) Analytic validation of immunohistochemical assays: a comparison of laboratory practices before and after introduction of an evidence-based guideline. Arch Pathol Lab Med 141(9):1247\u20131254. https:\/\/doi.org\/10.5858\/arpa.2016-0558-CP","journal-title":"Arch Pathol Lab Med"},{"key":"2976_CR26","volume-title":"ISO 15189:2012 Medical laboratories - Particular requirements for quality and competence","author":"International Organization for Standardization","year":"2012","unstructured":"International Organization for Standardization (2012) ISO 15189:2012 Medical laboratories - Particular requirements for quality and competence. ISO, Geneva"},{"issue":"Suppl1","key":"2976_CR27","doi-asserted-by":"publisher","first-page":"S7","DOI":"10.1016\/j.pathol.2017.12.012","volume":"50","author":"J Pagliuso","year":"2018","unstructured":"Pagliuso J (2018) The challenges of implementing a PD-L1 proficiency testing program and RCPAQAP update. Pathology 50(Suppl1):S7. https:\/\/doi.org\/10.1016\/j.pathol.2017.12.012","journal-title":"Pathology"},{"key":"2976_CR28","doi-asserted-by":"publisher","first-page":"138","DOI":"10.1002\/cjp2.153","volume":"6","author":"A Dodson","year":"2019","unstructured":"Dodson A, Parry S, Lissenberg-Witte B, Haragan A, Allen D, O'Grady A, McClean E, Hughes J, Miller K, Thunnissen E (2019) External quality assessment demonstrates that PD-L1 22C3 and SP263 assays are systematically different. J Pathol Clin Res. 6:138\u2013145. https:\/\/doi.org\/10.1002\/cjp2.153","journal-title":"J Pathol Clin Res."},{"key":"2976_CR29","unstructured":"Nordic Immunohistochemical Quality Control (2019) PD-L1 Run C5. https:\/\/www.nordiqc.org\/downloads\/assessments\/121_102.pdf."},{"issue":"5","key":"2976_CR30","doi-asserted-by":"publisher","first-page":"605","DOI":"10.1038\/s41416-018-0204-9","volume":"119","author":"V Tack","year":"2018","unstructured":"Tack V, Schuuring E, Keppens C, Hart N\u2019, Pauwels P, van Krieken H, Dequeker EMC (2018) Accreditation, setting and experience as indicators to assure quality in oncology biomarker testing laboratories. Br J Cancer 119(5):605\u2013614. https:\/\/doi.org\/10.1038\/s41416-018-0204-9","journal-title":"Br J Cancer"},{"key":"2976_CR31","volume-title":"ISO\/IEC 17043:2010 Conformity assessment - general requirements for proficiency testing","author":"International Organization for Standardisation","year":"2010","unstructured":"International Organization for Standardisation (2010) ISO\/IEC 17043:2010 Conformity assessment - general requirements for proficiency testing. ISO, Geneva"},{"issue":"2","key":"2976_CR32","doi-asserted-by":"publisher","first-page":"256","DOI":"10.1001\/jamaoncol.2016.3015","volume":"3","author":"P Gaule","year":"2017","unstructured":"Gaule P, Smithy JW, Toki M, Rehman J, Patell-Socha F, Cougot D, Collin P, Morrill P, Neumeister V, Rimm DL (2017) A quantitative comparison of antibodies to programmed cell death 1 ligand 1. JAMA Oncol 3(2):256\u2013259. https:\/\/doi.org\/10.1001\/jamaoncol.2016.3015","journal-title":"JAMA Oncol"},{"key":"2976_CR33","volume-title":"IASLC atlas of PD-L1 immunohistochemistry testing in lung cancer","author":"MSKK Tsao","year":"2017","unstructured":"Tsao MSKK, Dacic S, Yatabe Y, Hirsch FR (2017) IASLC atlas of PD-L1 immunohistochemistry testing in lung cancer. Editorial Rx Press, International Association for the Study of Lung Cancer"},{"issue":"12","key":"2976_CR34","doi-asserted-by":"publisher","first-page":"1564","DOI":"10.5858\/arpa.2014-0074-RA","volume":"138","author":"F Lin","year":"2014","unstructured":"Lin F, Chen Z (2014) Standardization of diagnostic immunohistochemistry: literature review and geisinger experience. Arch Pathol Lab Med 138(12):1564\u20131577. https:\/\/doi.org\/10.5858\/arpa.2014-0074-RA","journal-title":"Arch Pathol Lab Med"},{"issue":"12","key":"2976_CR35","doi-asserted-by":"publisher","first-page":"2241","DOI":"10.1016\/j.jtho.2016.07.012","volume":"11","author":"M Ibrahim","year":"2016","unstructured":"Ibrahim M, Parry S, Wilkinson D, Bilbe N, Allen D, Forrest S, Maxwell P, O'Grady A, Starczynski J, Tanier P, Gosney J, Kerr K, Miller K, Thunnissen E (2016) ALK immunohistochemistry in NSCLC: discordant staining can impact patient treatment regimen. J Thorac Oncol 11(12):2241\u20132247. https:\/\/doi.org\/10.1016\/j.jtho.2016.07.012","journal-title":"J Thorac Oncol"},{"key":"2976_CR36","volume-title":"Staining performance of ALK and ROS1 immunohistochemistry and influence on interpretation in NSCLC","author":"C Keppens","year":"2020","unstructured":"Keppens C, von der Th\u00fcsen JH, Pauwels P, Ryska A, \u2019tHart N, Schuuring E, Miller K, Thunnissen E, Zwaenepoel K, Dequeker EMC (2020) Staining performance of ALK and ROS1 immunohistochemistry and influence on interpretation in NSCLC. Submitted."},{"key":"2976_CR37","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1016\/j.humpath.2019.05.003","volume":"90","author":"E Munari","year":"2019","unstructured":"Munari E, Zamboni G, Lunardi G, Marconi M, Brunelli M, Martignoni G, Netto GJ, Quatrini L, Vacca P, Moretta L, Bogina G (2019) PD-L1 expression in non-small cell lung cancer: evaluation of the diagnostic accuracy of a laboratory-developed test using clone E1L3N in comparison with 22C3 and SP263 assays. Hum Pathol 90:54\u201359. https:\/\/doi.org\/10.1016\/j.humpath.2019.05.003","journal-title":"Hum Pathol"},{"key":"2976_CR38","unstructured":"Richards KL (2019) Complying With the new EU IVDR. https:\/\/www.precisionmedicinegrp.com\/pfm\/wp-content\/uploads\/sites\/3\/2018\/09\/Complying-With-the-new-EU-IVDR-Regulatory-Focus-2018-08.pdf."},{"issue":"10","key":"2976_CR39","doi-asserted-by":"publisher","first-page":"1384","DOI":"10.1097\/PAS.0000000000001105","volume":"42","author":"E Munari","year":"2018","unstructured":"Munari E, Rossi G, Zamboni G, Lunardi G, Marconi M, Sommaggio M, Netto GJ, Hoque MO, Brunelli M, Martignoni G, Haffner MC, Moretta F, Pegoraro MC, Cavazza A, Samogin G, Furlan V, Mariotti FR, Vacca P, Moretta L, Bogina G (2018) PD-L1 assays 22C3 and SP263 are not interchangeable in non-small cell lung cancer when considering clinically relevant cutoffs: an interclone evaluation by differently trained pathologists. Am J Surg Pathol 42(10):1384\u20131389. https:\/\/doi.org\/10.1097\/PAS.0000000000001105","journal-title":"Am J Surg Pathol"},{"issue":"2","key":"2976_CR40","doi-asserted-by":"publisher","first-page":"168","DOI":"10.1097\/00129039-200306000-00014","volume":"11","author":"CF Prinsen","year":"2003","unstructured":"Prinsen CF, Klaassen CH, Thunnissen FB (2003) Microarray as a model for quantitative visualization chemistry. Appl Immunohistochem Mol Morphol 11(2):168\u2013173. https:\/\/doi.org\/10.1097\/00129039-200306000-00014","journal-title":"Appl Immunohistochem Mol Morphol"},{"issue":"7","key":"2976_CR41","doi-asserted-by":"publisher","first-page":"1046","DOI":"10.3390\/ijms17071046","volume":"17","author":"G Botti","year":"2016","unstructured":"Botti G, Scognamiglio G, Cantile M (2016) PD-L1 immunohistochemical detection in tumor cells and tumor microenvironment: main considerations on the use of tissue micro arrays. Int J Mol Sci 17(7):1046. https:\/\/doi.org\/10.3390\/ijms17071046","journal-title":"Int J Mol Sci"},{"key":"2976_CR42","doi-asserted-by":"publisher","unstructured":"Keppens C, Tack V, \u2018t Hart N, Tembuyser L, Ryska A, Pauwels P, Zwaenepoel K, Schuuring E, Cabillic F, Tornillo L, Warth A, Weichert W, Dequeker E, EQA assessors expert group (2018) A stitch in time saves nine: external quality assessment rounds demonstrate improved quality of biomarker analysis in lung cancer. Oncotarget 9(29):20524-20538. https:\/\/doi.org\/10.18632\/oncotarget.24980","DOI":"10.18632\/oncotarget.24980"},{"issue":"1","key":"2976_CR43","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1097\/PAI.0000000000000163","volume":"23","author":"EE Torlakovic","year":"2015","unstructured":"Torlakovic EE, Nielsen S, Francis G, Garratt J, Gilks B, Goldsmith JD, Hornick JL, Hyjek E, Ibrahim M, Miller K, Petcu E, Swanson PE, Zhou X, Taylor CR, Vyberg M (2015) Standardization of positive controls in diagnostic immunohistochemistry: recommendations from the International Ad Hoc Expert Committee. Appl Immunohistochem Mol Morphol 23(1):1\u201318. https:\/\/doi.org\/10.1097\/PAI.0000000000000163","journal-title":"Appl Immunohistochem Mol Morphol"},{"issue":"2","key":"2976_CR44","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1097\/PAI.0000000000000444","volume":"25","author":"EE Torlakovic","year":"2017","unstructured":"Torlakovic EE, Cheung CC, D'Arrigo C, Dietel M, Francis GD, Gilks CB, Hall JA, Hornick JL, Ibrahim M, Marchetti A, Miller K, van Krieken JH, Nielsen S, Swanson PE, Vyberg M, Zhou X, Taylor CR, From the International Society for Immunohistochemistry and Molecular Morphology (ISIMM) and International Quality Network for Pathology (IQN Path) (2017) Evolution of quality assurance for clinical immunohistochemistry in the era of precision medicine\u2014part 2: immunohistochemistry test performance characteristics. Appl Immunohistochem Mol Morphol 25(2):79\u201385. https:\/\/doi.org\/10.1097\/PAI.0000000000000444","journal-title":"Appl Immunohistochem Mol Morphol"}],"container-title":["Virchows Archiv"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00428-020-02976-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00428-020-02976-5\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00428-020-02976-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,5,5]],"date-time":"2021-05-05T18:08:56Z","timestamp":1620238136000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00428-020-02976-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,12,4]]},"references-count":44,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2021,5]]}},"alternative-id":["2976"],"URL":"https:\/\/doi.org\/10.1007\/s00428-020-02976-5","relation":{},"ISSN":["0945-6317","1432-2307"],"issn-type":[{"value":"0945-6317","type":"print"},{"value":"1432-2307","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,12,4]]},"assertion":[{"value":"30 March 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 November 2020","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 November 2020","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 December 2020","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Compliance with ethical standards"}},{"order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"The samples originated from tissue blocks of leftover patient material obtained during routine care. Each scheme organizer signed a subcontractor agreement stating that the way in which the samples were obtained conformed to the national legal requirements for the use of patient samples. The samples were excluded from research regulations requiring informed consent.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics"}},{"value":"Virchows Archiv conforms to the ICMJE recommendation for qualification of authorship. The ICMJE recommends that authorship be based on the following 4 criteria:\n                      \n                      All individuals listed as co-authors of the manuscript must qualify for every one of the four criteria listed above. Should an individual\u2019s contributions to the manuscript meet three of the criteria or fewer, then they should not be listed as a co-author on the manuscript; instead, their contributions should be acknowledged in the Acknowledgements section of the manuscript.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical responsibilities of authors\u2019 section"}}]}}