{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T13:24:00Z","timestamp":1787664240805,"version":"build-2736575974"},"reference-count":39,"publisher":"Springer Science and Business Media LLC","issue":"9","license":[{"start":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T00:00:00Z","timestamp":1783382400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T00:00:00Z","timestamp":1783382400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Int J Clin Oncol"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>CLDN18.2-targeted therapies show promise in HER2-negative, CLDN18.2-positive advanced gastric cancer (GC); however, cutoffs defining CLDN18.2 positivity vary across studies. Tumors with high expression (moderate to strong membranous expression in\u2009\u2265\u200975% of tumor cells) generally exhibit intratumoral homogeneity and a uniform staining pattern, but intratumoral heterogeneity and staining pattern of CLDN18.2 at lower expression thresholds remains unclear. This study investigated intratumoral heterogeneity of CLDN18.2 by comparing inter-block concordance of expression levels and staining patterns in GC.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Eighty-six resected GC specimens were retrospectively analyzed using CLDN18.2 immunohistochemistry on two tissue blocks per tumor. CLDN18.2 expression was categorized as high (\u2265\u200975%), intermediate (&lt;\u200975% and\u2009\u2265\u200940%), or negative (&lt;\u200940%), and staining patterns as uniform or variable. Inter-block concordance of expression levels and staining patterns and their influence on concordance and outcomes were assessed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Overall inter-block concordance of expression levels was high (77%, \u03ba\u2009=\u20090.89). Discordance was substantially higher in intermediate expression tumors (63.5%) than in high (15.5%) or negative (19%) expression tumors. Uniform staining was observed exclusively in high expression tumors, whereas all intermediate expression tumors displayed variable staining (100%). Among high expression tumors, inter-block concordance was substantially higher with uniform staining (98.0%) than with variable staining (71.5%). CLDN18.2 expression and staining pattern heterogeneity were not associated with worse survival.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Significant intratumoral heterogeneity of CLDN18.2 expression was observed in GC, particularly in intermediate expression tumors; however, this heterogeneity does not affect survival. These results highlight the importance of standardized assessment methods when applying lower thresholds for CLDN18.2-targeted therapies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s10147-026-03118-8","type":"journal-article","created":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T16:07:52Z","timestamp":1783440472000},"page":"2033-2042","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Intratumoral heterogeneity of intermediate CLDN18.2 expression in gastric cancer"],"prefix":"10.1007","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-7176-821X","authenticated-orcid":false,"given":"Yusuke","family":"Kawanaka","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1282-232X","authenticated-orcid":false,"given":"Chiaki","family":"Inagaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masaki","family":"Okura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0033-8741","authenticated-orcid":false,"given":"Seiichiro","family":"Mitani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-1248-2558","authenticated-orcid":false,"given":"Naoki","family":"Shiraishi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1822-2720","authenticated-orcid":false,"given":"Kazuko","family":"Sakai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8275-0846","authenticated-orcid":false,"given":"Kazuto","family":"Nishio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0188-0586","authenticated-orcid":false,"given":"Yutaka","family":"Kimura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasutaka","family":"Chiba","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3328-5677","authenticated-orcid":false,"given":"Tomoko","family":"Wakasa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3280-4850","authenticated-orcid":false,"given":"Hisato","family":"Kawakami","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8787-5587","authenticated-orcid":false,"given":"Hidetoshi","family":"Hayashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,7,7]]},"reference":[{"issue":"3","key":"3118_CR1","doi-asserted-by":"publisher","first-page":"229","DOI":"10.3322\/caac.21834","volume":"74","author":"F Bray","year":"2022","unstructured":"Bray F, Laversanne M, Sung H et al (2022) Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. 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