{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,10]],"date-time":"2026-11-10T15:57:35Z","timestamp":1794326255238,"version":"4.9.0"},"reference-count":18,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,8,7]],"date-time":"2025-08-07T00:00:00Z","timestamp":1754524800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,8,7]],"date-time":"2025-08-07T00:00:00Z","timestamp":1754524800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100012681","name":"Universit\u00e4tsklinikum K\u00f6ln","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100012681","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Claudin 18.2 (CLDN18.2) is a therapeutically relevant biomarker in esophageal (EAC) -and gastric adenocarcinoma (GAC). Little is known about its heterogeneity within the primary tumor and corresponding metastases and how many biopsies are needed to determine the true CLDN18.2 status of a tumor. CLDN18.2 was assessed in 1,283 patients (822 EAC, 461 GAC), using the antibody clone 43\u201314\u00a0A. Eight virtual endoscopic biopsies were taken from digitized whole tumor blocks. 204 of 822 EAC (24.8%) and 132 of 461 GAC (28,6%) were positive for CLDN18.2. In GAC, CLDN18.2 expression showed a trend towards less invasive growth (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.02) and less common lymph node metastasis (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.07) and was more often observed within the EBV-associated subtype (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.01). When comparing the expression in one biopsy with the whole tissue section, the sensitivity for CLDN18.2 was low (58.8%). The sensitivity increased to a maximum of 76.5% with 6 and 8 biopsies (positive likelihood ratio\u2009=\u200917.8). Discordant expression between primary tumor and corresponding local lymph node metastasis was observed in 18.5%. This study highlights that CLDN18.2 is a heterogeneously expressed biomarker, within the tumor tissue as well as in primary tumor and corresponding lymph node metastasis. In case of CLN18.2-negative results the representativity of the biopsies must be critically assessed and a re-biopsy might be recommendable.\n                  <\/jats:p>","DOI":"10.1038\/s41598-025-12337-4","type":"journal-article","created":{"date-parts":[[2025,8,7]],"date-time":"2025-08-07T16:45:35Z","timestamp":1754585135000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["The expression of the tight junction protein and therapeutical target Claudin 18.2 is heterogeneously distributed within esophageal and gastric adenocarcinoma"],"prefix":"10.1038","volume":"15","author":[{"given":"Svetlana","family":"Pak","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrian Georg","family":"Simon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Su Ir","family":"Lyu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuri","family":"Tolkach","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hakan","family":"Alakus","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Zander","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reinhard","family":"Buettner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christiane Josephine","family":"Bruns","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wolfgang","family":"Schroeder","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Quaas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,8,7]]},"reference":[{"key":"12337_CR1","first-page":"17","volume":"73","author":"RL Siegel","year":"2023","unstructured":"Siegel, R. 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