{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T05:28:58Z","timestamp":1790659738212,"version":"4.1.0"},"reference-count":45,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2025,12,22]],"date-time":"2025-12-22T00:00:00Z","timestamp":1766361600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2025,12,22]],"date-time":"2025-12-22T00:00:00Z","timestamp":1766361600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Histopathology"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Claudin\u201018 (CLDN18) is both a marker for the gastric phenotype and a therapeutic target. However, little is known about its immunoexpression in endocervical adenocarcinomas (ECAs), particularly as detected using the clone 43\u201014A antibody, or about the gene expression of its isoforms in ECAs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>\n                      We examined CLDN18, HIK1083, p16 and Rb expression by immunohistochemistry and high\u2010risk human papillomavirus (HR\u2010HPV) mRNA by in situ hybridization (ISH) in 121 ECAs, including 35 HPV\u2010independent adenocarcinomas (gastric type [GAS],\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200924; non\u2010GAS,\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200911) and 86 HPV\u2010associated ECAs. We also analysed mRNA expression of the\n                      <jats:italic>CLDN18.1<\/jats:italic>\n                      (lung type) and\n                      <jats:italic>CLDN18.2<\/jats:italic>\n                      (gastric type) isoforms by quantitative polymerase chain reaction (qPCR) in selected cases. CLDN18 positivity was detected in 8\/24 (33%) GASs, 0\/11 (0%) non\u2010GASs and 2\/86 (2%) HPV\u2010associated ECAs, with positivity defined as staining in \u226575% of tumour cells, as in gastric cancer. When a 5% cut\u2010off was used, CLDN18 positivity was detected in 22\/24 (92%) GASs, 0\/11 (0%) non\u2010GASs and 6\/86 (7%) HPV\u2010associated ECAs; CLDN18 expression was thus significantly associated with GAS histology (\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&lt;\u20090.0001). Among the 6 cases of HPV\u2010associated ECAs with CLDN18 expression (ranging from 5% to 80%), the histological patterns included a mix of usual and mucinous features in 4 cases, pure usual type in 1 and villoglandular variant in 1. Otherwise features such as p16 overexpression and the Rb partial loss pattern were consistent with those of HPV\u2010associated ECAs. Six of 22 (27%) CLDN18\u2010positive GASs were also positive for p16, but their other features\u2014such as CLDN18 expression and the Rb preserved pattern\u2014were the same as in p16 negative GASs. Expression of\n                      <jats:italic>CLDN18.2<\/jats:italic>\n                      mRNA but not\n                      <jats:italic>CLDN18.1<\/jats:italic>\n                      mRNA was confirmed in both GASs and HPV\u2010associated ECAs.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      CLDN18 (43\u201014A) emerged as a potential diagnostic and therapeutic marker for GAS. A minor subset of HPV\u2010associated ECAs also can be immunoreactive for CLDN18 and express\n                      <jats:italic>CLDN18.2<\/jats:italic>\n                      mRNA, suggesting divergent gastric phenotypic differentiation. The caution is that GAS and HPV\u2010associated ECAs can share overlapping histological features and similar expression of CLDN18 and p16.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/his.70066","type":"journal-article","created":{"date-parts":[[2025,12,22]],"date-time":"2025-12-22T10:01:53Z","timestamp":1766397713000},"page":"1003-1015","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Claudin\u201018 expression in gastric type adenocarcinoma and\n                    <scp>HPV<\/scp>\n                    \u2010associated adenocarcinoma of the uterine cervix"],"prefix":"10.1111","volume":"88","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3092-969X","authenticated-orcid":false,"given":"Nobuko","family":"Yasutake","sequence":"first","affiliation":[{"name":"Department of Gynecology and Obstetrics, Graduate School of Medical Sciences Kyushu University  Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-8480-5010","authenticated-orcid":false,"given":"Yuki","family":"Yokawa","sequence":"additional","affiliation":[{"name":"Department of Pathology and Oncology, Graduate School of Medicine, Dentistry &amp; Pharmaceutical Science Okayama University  Okayama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1509-5706","authenticated-orcid":false,"given":"Takehiro","family":"Tanaka","sequence":"additional","affiliation":[{"name":"Department of Pathology and Oncology, Graduate School of Medicine, Dentistry &amp; Pharmaceutical Science Okayama University  Okayama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-4298-1381","authenticated-orcid":false,"given":"Riri","family":"Mishima","sequence":"additional","affiliation":[{"name":"Department of Pathology and Oncology, Graduate School of Medicine, Dentistry &amp; Pharmaceutical Science Okayama University  Okayama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-8170-2660","authenticated-orcid":false,"given":"Misato","family":"Komamizu","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, Graduate School of Medical Sciences Kyushu University  Fukuoka Japan"},{"name":"Department of Anatomic Pathology, Pathological Sciences, Graduate School of Medical Sciences Kyushu University  Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-5369-4615","authenticated-orcid":false,"given":"Ryosuke","family":"Kuga","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Graduate School of Medical Sciences Kyushu University  Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3826-6870","authenticated-orcid":false,"given":"Rina","family":"Jiromaru","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Graduate School of Medical Sciences Kyushu University  Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5811-4834","authenticated-orcid":false,"given":"Shinichiro","family":"Kawatoko","sequence":"additional","affiliation":[{"name":"Department of Medicine and Clinical Science Kyushu University Beppu Hospital  Beppu Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9887-3923","authenticated-orcid":false,"given":"Kenzo","family":"Sonoda","sequence":"additional","affiliation":[{"name":"Department of Gynecology Kyushu University Beppu Hospital  Beppu Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3142-8993","authenticated-orcid":false,"given":"Hideaki","family":"Yahata","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, Graduate School of Medical Sciences Kyushu University  Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0047-7637","authenticated-orcid":false,"given":"Kiyoko","family":"Kato","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, Graduate School of Medical Sciences Kyushu University  Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9636-1182","authenticated-orcid":false,"given":"Yoshinao","family":"Oda","sequence":"additional","affiliation":[{"name":"Department of Anatomic Pathology, Pathological Sciences, Graduate School of Medical Sciences Kyushu University  Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9148-6445","authenticated-orcid":false,"given":"Hidetaka","family":"Yamamoto","sequence":"additional","affiliation":[{"name":"Department of Pathology and Oncology, Graduate School of Medicine, Dentistry &amp; 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