{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T17:09:29Z","timestamp":1772989769371,"version":"3.50.1"},"reference-count":27,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2025,12,9]],"date-time":"2025-12-09T00:00:00Z","timestamp":1765238400000},"content-version":"vor","delay-in-days":8,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T00:00:00Z","timestamp":1764547200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100002951","name":"Dokkyo Medical University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002951","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["APMIS"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    This study was conducted to determine the frequency of high\u2010grade pancreatic intraepithelial lesions (HG\u2010PanIN) and the cancerization of ducts (COD), a phenomenon in which invasive cancer spreads within the pancreatic duct, and the differences between mucous profiles in pancreatic ductal adenocarcinoma. Immunohistochemistry for p53, SMAD4 and mucin was performed on 103 lesions in 97 cases. Carcinoma in\u00a0situ (CIS) with p53 and SMAD4 staining that were different from invasive carcinoma were classified as HG\u2010PanIN, while CIS with staining consistent with invasive carcinoma were classified as COD. CIS lesions were classified as 63 COD (61.2%) and 29 HG\u2010PanIN (28.2%). The CODs consisted of 30 lesions (47.6%) with aberrant p53 and SMAD4, 26 lesions (41.3%) with aberrant p53, and 7 lesions (11.1%) with aberrant SMAD4. Fourteen HG\u2010PanIN lesions (48.3%) had aberrant p53. MUC1 positivity was lower in COD (27 lesions; 42.9%) and HG\u2010PanIN (16 lesions; 55.2%) than in invasive carcinoma (81 lesions; 83.5%) (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.01). MUC6 was positive in 17 HG\u2010PanIN lesions (58.6%)\u2014higher than in invasive carcinoma (18\u00a0lesions; 18.6%) and COD (8 lesions; 12.7%) (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.001). This study classified CIS as COD and HG\u2010PanIN and found that the MUC6 expression of COD and HG\u2010PanIN differed.\n                  <\/jats:p>","DOI":"10.1111\/apm.70106","type":"journal-article","created":{"date-parts":[[2025,12,9]],"date-time":"2025-12-09T08:04:29Z","timestamp":1765267469000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Immunohistochemical Classification of High\u2010Grade Pancreatic Intraepithelial Neoplasia and Ductal Cancerization in Pancreatic Ductal Adenocarcinoma Using\u00a0p53,\n                    <scp>SMAD4<\/scp>\n                    , and Mucin Expression"],"prefix":"10.1111","volume":"133","author":[{"given":"Yumi","family":"Nozawa\u2010Yoshimura","sequence":"first","affiliation":[{"name":"Department of Diagnostic Pathology Dokkyo Medical University  Mibu Tochigi Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2804-4588","authenticated-orcid":false,"given":"Kazuyuki","family":"Ishida","sequence":"additional","affiliation":[{"name":"Department of Diagnostic Pathology Dokkyo Medical University  Mibu Tochigi Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masato","family":"Onozaki","sequence":"additional","affiliation":[{"name":"Department of Diagnostic Pathology Dokkyo Medical University  Mibu Tochigi Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Akihiro","family":"Kawabe","sequence":"additional","affiliation":[{"name":"Department of Diagnostic Pathology Dokkyo Medical University  Mibu Tochigi Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Taku","family":"Aoki","sequence":"additional","affiliation":[{"name":"Department of Hepato\u2010Biliary\u2010Pancreatic Surgery Dokkyo Medical University  Mibu Tochigi Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,12,9]]},"reference":[{"key":"e_1_2_11_2_1","volume-title":"Digestive System Tumours","author":"Hruban R. 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