{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T20:15:13Z","timestamp":1792008913284,"version":"4.4.0"},"reference-count":20,"publisher":"SAGE Publications","issue":"10","license":[{"start":{"date-parts":[[2011,8,10]],"date-time":"2011-08-10T00:00:00Z","timestamp":1312934400000},"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":["J Histochem Cytochem."],"published-print":{"date-parts":[[2011,10]]},"abstract":"<jats:p>Pancreatic ductal neoplasms exhibit gastric epithelium\u2013like characteristics. In this study, we evaluated the expression of claudin-18 (CLDN18), a gastric epithelium\u2013associated claudin, in pancreatic intraepithelial neoplasias (PanINs), intraductal papillary mucinous neoplasms (IPMNs), mucinous cystic neoplasms (MCNs), and pancreatic ductal adenocarcinomas (PDACs) using immunohistochemistry. We observed a high level of expression of CLDN18 in PanINs (31\/32, 97%), IPMNs (61\/65, 95%), and MCNs (4\/5, 80%) using ordinary tissue section analysis. Furthermore, we observed a high level of CLDN18 expression in PDACs (109\/156, 70%) using tissue microarray analysis. However, the normal pancreatic duct or the ductal metaplasia of the acinar cells was not immunoreactive. Comparative analysis of CLDN18 and phenotypic markers in IPMNs revealed that simultaneous expression of CLDN18 and intestinal markers frequently occurred, even in intestinal-type IPMNs. CLDN18 variant 2 mRNA was expressed and was similarly upregulated by phorbol 12\u2013myristate 13\u2013acetate (PMA) treatment in pancreatic cancer cell lines and in a gastric cancer cell line. An inhibitor of pan-PKC (GF109203X) completely suppressed this upregulation in pancreatic cancer cells. These results indicate that CLDN18, a marker for the early carcinogenetic process, is commonly expressed in precursor lesions of PDAC. Activation of the PKC pathway might be involved in CLDN18 expression associated with pancreatic carcinogenesis.<\/jats:p>","DOI":"10.1369\/0022155411420569","type":"journal-article","created":{"date-parts":[[2011,8,11]],"date-time":"2011-08-11T13:46:18Z","timestamp":1313070378000},"page":"942-952","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":105,"title":["Claudin-18 Is an Early-Stage Marker of Pancreatic Carcinogenesis"],"prefix":"10.1177","volume":"59","author":[{"given":"Mariko","family":"Tanaka","sequence":"first","affiliation":[{"name":"Department of Pathology (MT,JS,AS,MU,SI,MF) Graduate School of Medicine, The University of Tokyo, Tokyo, Japan"},{"name":"Department of Surgery (NK) Graduate School of Medicine, The University of Tokyo, Tokyo, Japan"},{"name":"Department of Diagnostic Pathology, Jichi Medical University Hospital, Tochigi, Japan (NF)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junji","family":"Shibahara","sequence":"additional","affiliation":[{"name":"Department of Pathology (MT,JS,AS,MU,SI,MF) Graduate School of Medicine, The University of Tokyo, Tokyo, Japan"},{"name":"Department of Surgery (NK) Graduate School of Medicine, The University of Tokyo, Tokyo, Japan"},{"name":"Department of Diagnostic Pathology, Jichi Medical University Hospital, Tochigi, Japan (NF)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noriyoshi","family":"Fukushima","sequence":"additional","affiliation":[{"name":"Department of Pathology (MT,JS,AS,MU,SI,MF) Graduate School of Medicine, The University of Tokyo, Tokyo, Japan"},{"name":"Department of Surgery (NK) Graduate School of Medicine, The University of Tokyo, Tokyo, Japan"},{"name":"Department of Diagnostic Pathology, Jichi Medical University Hospital, Tochigi, Japan (NF)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aya","family":"Shinozaki","sequence":"additional","affiliation":[{"name":"Department of Pathology (MT,JS,AS,MU,SI,MF) Graduate School of Medicine, The University of Tokyo, Tokyo, Japan"},{"name":"Department of Surgery (NK) Graduate School of Medicine, The University of Tokyo, Tokyo, Japan"},{"name":"Department of Diagnostic Pathology, Jichi Medical University Hospital, Tochigi, Japan (NF)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Makoto","family":"Umeda","sequence":"additional","affiliation":[{"name":"Department of Pathology (MT,JS,AS,MU,SI,MF) Graduate School of Medicine, The University of Tokyo, Tokyo, Japan"},{"name":"Department of Surgery (NK) Graduate School of Medicine, The University of Tokyo, Tokyo, Japan"},{"name":"Department of Diagnostic Pathology, Jichi Medical University Hospital, Tochigi, Japan 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(NF)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masashi","family":"Fukayama","sequence":"additional","affiliation":[{"name":"Department of Pathology (MT,JS,AS,MU,SI,MF) Graduate School of Medicine, The University of Tokyo, Tokyo, Japan"},{"name":"Department of Surgery (NK) Graduate School of Medicine, The University of Tokyo, Tokyo, Japan"},{"name":"Department of Diagnostic Pathology, Jichi Medical University Hospital, Tochigi, Japan (NF)"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2011,8,10]]},"reference":[{"key":"bibr1-0022155411420569","doi-asserted-by":"publisher","DOI":"10.1097\/01.pas.0000213305.98187.d4"},{"key":"bibr2-0022155411420569","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0b013e3181cf8bb6"},{"key":"bibr3-0022155411420569","doi-asserted-by":"publisher","DOI":"10.1007\/s00428-005-0039-7"},{"key":"bibr4-0022155411420569","volume-title":"Tumors of the Digestive 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