{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T14:02:24Z","timestamp":1789912944886,"version":"4.0.1"},"reference-count":56,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T00:00:00Z","timestamp":1789689600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Int J Surg Pathol"],"abstract":"<jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Biliary tract cancers (BTCs) have dismal outcomes and limited validated predictive biomarkers. We investigated the immunohistochemical expression of CLDN18, PD-L1, and HER2 in resected gallbladder and biliary tract adenocarcinomas and evaluated their associations with clinicopathologic features and survival outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Fifty-three surgically resected adenocarcinomas from the gallbladder (\n                      <jats:italic toggle=\"yes\">n<\/jats:italic>\n                      \u2005=\u200526) and biliary tract (extrahepatic cholangiocarcinoma (eCCA) (\n                      <jats:italic toggle=\"yes\">n<\/jats:italic>\n                      \u2005=\u200525), intrahepatic cholangiocarcinoma (iCCA) (\n                      <jats:italic toggle=\"yes\">n<\/jats:italic>\n                      \u2005=\u20052)). Whole-tissue sections were stained for CLDN18.2, PD-L1 (SP263), and HER2. CLDN18 expression was defined as any unequivocal membranous staining; high-level positivity was defined as moderate-strong (2+\/3+) membranous staining in \u226575% of tumor cells. PD-L1 was scored by TPS and CPS (CPS \u22651 positive).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      CLDN18 expression was detected in 28\/53 (53%) and was more frequent in gallbladder carcinoma (GBC) than non-gallbladder tumors (\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      \u2005=\u2005.05); high-level CLDN18 positivity was present in 11\/53 (21%). PD-L1 positivity was infrequent by TPS (5\/53, 9%) but higher by CPS (19\/53, 36%); all TPS-positive tumors occurred in the GBC subgroup. HER2 immunoreactivity was observed in 7\/53 (13%), predominantly low-level. CLDN18 expression and high-level positivity were associated with improved DFS (\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      \u2005=\u2005.028 and\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      \u2005=\u2005.009) and RFS (\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      \u2005=\u2005.031 and\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      \u2005=\u2005.035). In multivariable models, margin positivity independently predicted worse OS and DFS (OS HR \u223c3.5; DFS HR 3.17), while high-level CLDN18 independently predicted improved DFS (HR 0.27). PD-L1 and HER2 showed limited survival discrimination overall.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>High-level CLDN18 positivity identifies a prognostically favorable subset of resected BTC, independently associated with lower recurrence risk. These findings support CLDN18.2 as a clinically relevant biomarker for risk stratification and potential trial selection, warranting prospective multicenter validation with standardized scoring and sampling strategies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/10668969261477760","type":"journal-article","created":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T13:43:33Z","timestamp":1789739013000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Claudin 18.2 Expression and Outcomes in Resected Gallbladder and Biliary Tract Adenocarcinomas: A Pilot Clinicopathologic Study"],"prefix":"10.1177","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2558-786X","authenticated-orcid":false,"given":"Irem","family":"Guvendir Bakkaloglu","sequence":"first","affiliation":[{"name":"Department of Pathology, Kartal Dr. L\u00fctfi K\u0131rdar City Hospital, Istanbul, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6655-1014","authenticated-orcid":false,"given":"Ilkay","family":"Tosun","sequence":"additional","affiliation":[{"name":"Department of Pathology, \u00dcmraniye Training and Research Hospital, University of Health Sciences, Istanbul, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3688-2768","authenticated-orcid":false,"given":"Gizem","family":"\u0130ssin","sequence":"additional","affiliation":[{"name":"Department of Pathology, Faculty of Medicine, \u00c7anakkale Onsekiz Mart University, \u00c7anakkale, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nihat Bu\u011fra","family":"A\u011fao\u011flu","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics, \u00dcmraniye Training and Research Hospital, University of Health Sciences, Istanbul, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3099-5307","authenticated-orcid":false,"given":"Onur","family":"\u015eahin","sequence":"additional","affiliation":[{"name":"Department of Pathology, \u00dcmraniye Training and Research Hospital, University of Health Sciences, Istanbul, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bilge","family":"Konuk","sequence":"additional","affiliation":[{"name":"Department of Pathology, Kocaeli City Hospital, Izmit, Kocaeli, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melike","family":"\u00d6z\u00e7elik","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, \u00dcmraniye Training and Research Hospital, University of Health Sciences, Istanbul, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"It\u0131r Ebru","family":"Zemheri","sequence":"additional","affiliation":[{"name":"Department of Pathology, \u00dcmraniye Training and Research Hospital, University of Health Sciences, Istanbul, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,9,18]]},"reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.humpath.2024.07.001"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00428-022-03482-6"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.critrevonc.2016.08.013"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00432-024-05975-0"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2022.935340"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.path.2018.02.005"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1053\/j.semdp.2012.08.010"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1111\/liv.14089"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrgastro.2016.51"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1097\/01.sla.0000251366.62632.d3"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2019.03.013"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2011.12.005"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.prp.2024.155145"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41416-019-0508-4"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.modpat.2024.100589"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1111\/his.13669"},{"key":"e_1_3_2_18_2","doi-asserted-by":"crossref","unstructured":"Amin M Edge S Greene F et al. 2017. 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