{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T23:09:43Z","timestamp":1787785783612,"version":"build-2784847793"},"reference-count":19,"publisher":"Springer Science and Business Media LLC","issue":"5","license":[{"start":{"date-parts":[[2025,6,28]],"date-time":"2025-06-28T00:00:00Z","timestamp":1751068800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,6,28]],"date-time":"2025-06-28T00:00:00Z","timestamp":1751068800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Universit\u00e4tsklinikum Schleswig-Holstein - Campus Kiel"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Virchows Arch"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Biomarker testing is vital for personalized cancer treatment with improved efficacy based on genotype and biomarker expression. This prospective, in vitro, non-interventional study accompanied an independent proficiency test to descriptively analyze the results of immunohistochemical claudin 18.2 (CLDN18.2) testing in gastric cancer tissue samples by laboratories in Germany, Austria, and Switzerland, using assays independently established in their institutions. CLDN18.2 is a biomarker and drug target for locally advanced unresectable\/metastatic gastric and pancreatic cancer. During an open proficiency test (OPT), laboratories were provided with 10 gastric cancer tissue samples (cases) for staining, interpretation, and scoring by a pathologist. Results were submitted with stained tumor cell percentage and a binary CLDN18.2-positive\/negative result for each sample (cut-off:\u2009\u2265\u200975% of tumor cells expressing membranous CLDN18 with\u2009\u2265\u20092+\u2009[moderate to strong] staining intensity). Successful participation was defined as\u2009\u2265\u200990% of cases evaluated correctly. Overall proficiency of the OPT was acceptable if\u2009\u2265\u200980% of laboratories participated successfully. Fifty-four institutes registered for the OPT, and one resigned. Forty-two of 53 (79.2%) institutes participated successfully. The main source of errors was false negative results (false negative rate, 12%; false positive rate, 1%). Overall accuracy was 91%. The CLDN18 (43-14A) clone was used most frequently, with optimal staining results and minor interpretation problems observed. Two antibodies were associated with false negative results (ZR451 [Zeta\/Zytomed]; EPR19202 [Abcam]). Staining quality was the major factor for successful analysis; interpretation errors were not significant. Ongoing quality assurance will enable establishment of appropriate staining protocols and accurate CLDN18.2 interpretation, thereby facilitating individually optimized treatment.<\/jats:p>","DOI":"10.1007\/s00428-025-04138-x","type":"journal-article","created":{"date-parts":[[2025,6,27]],"date-time":"2025-06-27T22:13:54Z","timestamp":1751062434000},"page":"1117-1125","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Concordance of laboratory assays for claudin 18.2 in gastric cancer tissue samples: independent proficiency testing and a descriptive non-interventional study"],"prefix":"10.1007","volume":"487","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6989-8002","authenticated-orcid":false,"given":"Christoph","family":"R\u00f6cken","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne Kathrin","family":"H\u00f6hn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9200-441X","authenticated-orcid":false,"given":"Jens","family":"Neumann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9856-7050","authenticated-orcid":false,"given":"Hans-Ulrich","family":"Schildhaus","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4775-6609","authenticated-orcid":false,"given":"Stephan","family":"Singer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Till S.","family":"Clauditz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Quaas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Korinna","family":"J\u00f6hrens","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,6,28]]},"reference":[{"key":"4138_CR1","doi-asserted-by":"publisher","first-page":"229","DOI":"10.3322\/caac.21834","volume":"74","author":"F Bray","year":"2024","unstructured":"Bray F, Laversanne M, Sung H, Ferlay J, Siegel RL, Soerjomataram I, Jemal A (2024) Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. 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Front Immunol 10:1441. https:\/\/doi.org\/10.3389\/fimmu.2019.01441","journal-title":"Front Immunol"},{"key":"4138_CR5","doi-asserted-by":"publisher","first-page":"257","DOI":"10.1038\/s41416-019-0508-4","volume":"121","author":"I Coati","year":"2019","unstructured":"Coati I, Lotz G, Fanelli GN, Brignola S, Lanza C, Cappellesso R, Pellino A, Pucciarelli S, Spolverato G, Guzzardo V, Munari G, Zaninotto G, Scarpa M, Mastracci L, Farinati F, Realdon S, Pilati P, Lonardi S, Valeri N, Rugge M, Kiss A, Loupakis F, Fassan M (2019) Claudin-18 expression in oesophagogastric adenocarcinomas: a tissue microarray study of 523 molecularly profiled cases. 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The study utilized formalin-fixed paraffin-embedded gastric cancer resection samples obtained by QuIP from a non-commercial supplier blind to patient information. Ethical approval was obtained from the local ethics committee (D593\/23 [22.09.2023]) of the University Hospital Schleswig-Holstein, Kiel, Germany.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical conduct"}},{"value":"CR received honoraria from Alnylam, Astellas, BMS, Janssen, MSD, and Pfizer for lectures and advisory board memberships. AKH, KJ, TSC, and SS have no conflicts to disclose. JN was involved in advisory boards and received honoraria for lectures from Agilent, Astellas, BMS, Boehringer, Falk, MSD, Pierre Fabre, and Roche. H-US is an employee of Discovery Life Sciences and was involved in advisory boards, research, and service projects with pharmaceutical companies as part of this work; payments from Astellas, BMS, Daiichi Sankyo, GSK, MSD, Roche, and Zytomics have been made to the employer. AQ reports payment for lectures by Astellas Pharma, Inc.; travel support for in-office meeting by Astellas Pharma, Inc.; and advisory board participation for Astellas Pharma, Inc.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflicts of interest"}}]}}