{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T22:43:30Z","timestamp":1792190610092,"version":"4.4.0"},"reference-count":28,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2020,3,10]],"date-time":"2020-03-10T00:00:00Z","timestamp":1583798400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP16H05410"],"award-info":[{"award-number":["JP16H05410"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["pathsocjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pathology"],"published-print":{"date-parts":[[2020,5]]},"abstract":"Abstract<\/jats:title>\n \n Intraductal papillary neoplasm of the bile duct (IPNB) is a grossly visible papillary biliary neoplasm with morphological variations and occasional invasion. Recently a new classification of IPNB into type 1 and type 2 was proposed in which the type 1 IPNBs consist of fine papillary neoplastic glands and the type 2 IPNBs consist of complex branching glands, seldom with foci of solid\u2010tubular components. However, clinicopathological and molecular characteristics of these types of IPNBs are yet to be identified. We aimed to uncover clinicopathological and molecular characteristics of the types of IPNBs. Thirty\u2010six IPNBs were studied retrospectively. Clinicopathological features as well as molecular alterations of 31 genes were evaluated by means of targeted next\u2010generation sequencing and immunohistochemical examination of expression of mucin and cancer\u2010associated molecules. The 36 IPNBs were classified into 22 of type 1 and 14 of type 2. The type 1 IPNBs were associated with a non\u2010invasive phenotype, intestinal and oncocytic subtypes, development in the intrahepatic bile duct, overt mucin production, and a relatively good prognosis. The type 2 IPNBs were associated with an invasive phenotype, the pancreatobiliary subtype, development within the extrahepatic bile duct, and worse prognosis compared with the type 1 IPNBs. In the molecular analysis, recurrent mutations were found in\n TP53<\/jats:italic>\n (34.3%),\n KRAS<\/jats:italic>\n (31.4%),\n STK11<\/jats:italic>\n (25.7%),\n CTNNB1<\/jats:italic>\n (17.1%),\n APC<\/jats:italic>\n (14.3%),\n SMAD4<\/jats:italic>\n (14.3%),\n GNAS<\/jats:italic>\n (11.4%),\n PBRM1<\/jats:italic>\n (11.4%),\n ELF3<\/jats:italic>\n (8.6%),\n KMT2C<\/jats:italic>\n (8.6%),\n NF1<\/jats:italic>\n (8.6%),\n PIK3CA<\/jats:italic>\n (8.6%),\n ARID1A<\/jats:italic>\n (5.7%),\n ARID2<\/jats:italic>\n (5.7%),\n BAP1<\/jats:italic>\n (5.7%),\n BRAF<\/jats:italic>\n (5.7%),\n EPHA6<\/jats:italic>\n (5.7%),\n ERBB2<\/jats:italic>\n (5.7%),\n ERBB3<\/jats:italic>\n (5.7%),\n KMT2D<\/jats:italic>\n (5.7%), and\n RNF43<\/jats:italic>\n (5.7%). Mutations in\n KRAS<\/jats:italic>\n and\n GNAS<\/jats:italic>\n were enriched in the type 1 IPNBs, whereas mutations in\n TP53<\/jats:italic>\n ,\n SMAD4<\/jats:italic>\n , and\n KMT2C<\/jats:italic>\n were enriched in the type 2 IPNBs. These results indicate that IPNBs consist of two distinct types of neoplasms specifically associated with clinicopathological features and molecular phenotypes. \u00a9 2020 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.\n <\/jats:p>","DOI":"10.1002\/path.5398","type":"journal-article","created":{"date-parts":[[2020,2,26]],"date-time":"2020-02-26T05:26:21Z","timestamp":1582694781000},"page":"38-48","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":58,"title":["Intraductal papillary neoplasms of the bile duct consist of two distinct types specifically associated with clinicopathological features and molecular phenotypes"],"prefix":"10.1002","volume":"251","author":[{"given":"Yasutaka","family":"Aoki","sequence":"first","affiliation":[{"name":"Department of Surgery Tohoku University Graduate School of Medicine Sendai Japan"},{"name":"Department of Investigative Pathology Tohoku University Graduate School of Medicine Sendai Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masamichi","family":"Mizuma","sequence":"additional","affiliation":[{"name":"Department of Surgery Tohoku University Graduate School of Medicine Sendai Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatsuo","family":"Hata","sequence":"additional","affiliation":[{"name":"Department of Surgery Tohoku University Graduate School of Medicine Sendai Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeshi","family":"Aoki","sequence":"additional","affiliation":[{"name":"Department of Surgery Tohoku University Graduate School of Medicine Sendai Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuko","family":"Omori","sequence":"additional","affiliation":[{"name":"Department of Investigative Pathology Tohoku University Graduate School of Medicine Sendai Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yusuke","family":"Ono","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Research, Sapporo Higashi Tokushukai Hospital Sapporo 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Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,3,10]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1053\/jhep.2001.28199"},{"key":"e_1_2_8_3_1","first-page":"217","volume-title":"World Health Organizaion Classification of Tumours of the Digestive System","author":"Nakanuma Y","year":"2010"},{"key":"e_1_2_8_4_1","first-page":"266","volume-title":"World Health Organizaion Classification of Tumours of the Digestive System","author":"Albores\u2010Saavedra J","year":"2010"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00428-017-2144-9"},{"key":"e_1_2_8_6_1","first-page":"3112","article-title":"Clinicopathological characterization of so\u2010called \"cholangiocarcinoma with intraductal papillary growth\" with respect to \"intraductal papillary neoplasm of bile duct (IPNB)\"","volume":"7","author":"Nakanuma Y","year":"2014","journal-title":"Int J Clin Exp 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