{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T01:49:55Z","timestamp":1790819395125,"version":"4.1.0"},"reference-count":32,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2013,10,9]],"date-time":"2013-10-09T00:00:00Z","timestamp":1381276800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["pathsocjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pathology"],"published-print":{"date-parts":[[2013,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p><jats:bold>Intraductal tubulopapillary neoplasms (<jats:styled-content style=\"fixed-case\">ITPNs<\/jats:styled-content>) are composed of tubulopapillary glands with high\u2010grade dysplasia in the pancreatic duct. Intraductal papillary mucinous neoplasms of the gastric type, pyloric gland variant (<jats:styled-content style=\"fixed-case\">IPMN\u2010PGs<\/jats:styled-content>) are composed of tubular glands mimicking pyloric glands with low\u2010grade dysplasia and were formerly called intraductal tubular adenomas. Because of their apparent common tubular morphology, <jats:styled-content style=\"fixed-case\">IPMN\u2010PGs<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">ITPNs<\/jats:styled-content> could be associated. While the former might progress to the latter, this has not been fully assessed. In this study, we compared the molecular features of <jats:styled-content style=\"fixed-case\">ITPNs<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">IPMN\u2010PGs<\/jats:styled-content> to determine their association using formalin\u2010fixed, paraffin\u2010embedded tissues of 14 <jats:styled-content style=\"fixed-case\">ITPNs<\/jats:styled-content> and 15 <jats:styled-content style=\"fixed-case\">IPMN\u2010PGs<\/jats:styled-content>. Somatic mutations in <jats:italic><jats:styled-content style=\"fixed-case\">PIK3CA<\/jats:styled-content><\/jats:italic>, <jats:italic><jats:styled-content style=\"fixed-case\">GNAS<\/jats:styled-content><\/jats:italic>, <jats:italic><jats:styled-content style=\"fixed-case\">KRAS<\/jats:styled-content><\/jats:italic>, and <jats:italic><jats:styled-content style=\"fixed-case\">BRAF<\/jats:styled-content><\/jats:italic> were determined by Sanger sequencing. Expression of phosphorylated <jats:styled-content style=\"fixed-case\">AKT<\/jats:styled-content> was examined by immunohistochemistry. Somatic <jats:italic><jats:styled-content style=\"fixed-case\">PIK3CA<\/jats:styled-content><\/jats:italic> mutations were found in 3 of 14 <jats:styled-content style=\"fixed-case\">ITPNs<\/jats:styled-content> (21.4%) but in none of the <jats:styled-content style=\"fixed-case\">IPMN\u2010PGs<\/jats:styled-content> (<jats:italic>p<\/jats:italic> = 0.0996). In contrast, <jats:italic><jats:styled-content style=\"fixed-case\">GNAS<\/jats:styled-content><\/jats:italic> mutations were found in none of the <jats:styled-content style=\"fixed-case\">ITPNs<\/jats:styled-content> but in 9 of 15 <jats:styled-content style=\"fixed-case\">IPMN\u2010PGs<\/jats:styled-content> (60.0%; <jats:italic>p<\/jats:italic> &lt; 0.001). <jats:italic><jats:styled-content style=\"fixed-case\">KRAS<\/jats:styled-content><\/jats:italic> mutations were detected in 1 of 14 <jats:styled-content style=\"fixed-case\">ITPNs<\/jats:styled-content> (7.1%) and 12 of 15 <jats:styled-content style=\"fixed-case\">IPMN\u2010PGs<\/jats:styled-content> (80.0%; <jats:italic>p<\/jats:italic> &lt; 0.001). <jats:italic><jats:styled-content style=\"fixed-case\">BRAF<\/jats:styled-content><\/jats:italic> mutation was found in one <jats:styled-content style=\"fixed-case\">ITPN<\/jats:styled-content> but in none of the <jats:styled-content style=\"fixed-case\">IPMN\u2010PGs<\/jats:styled-content>. Phosphorylated <jats:styled-content style=\"fixed-case\">AKT<\/jats:styled-content> expression in <jats:styled-content style=\"fixed-case\">ITPNs<\/jats:styled-content> was significantly more evident than that in <jats:styled-content style=\"fixed-case\">IPMN\u2010PGs<\/jats:styled-content> (<jats:italic>p<\/jats:italic> = 0.0401). These results indicate that <jats:styled-content style=\"fixed-case\">ITPNs<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">IPMN\u2010PGs<\/jats:styled-content> are molecularly distinct, suggesting that <jats:styled-content style=\"fixed-case\">IPMN\u2010PG<\/jats:styled-content> does not progress to <jats:styled-content style=\"fixed-case\">ITPN<\/jats:styled-content>. Furthermore, the molecular features of <jats:styled-content style=\"fixed-case\">IPMN\u2010PGs<\/jats:styled-content> are confirmed to be identical to those of <jats:styled-content style=\"fixed-case\">IPMNs<\/jats:styled-content> reported elsewhere. These results validate the current World Health Organization system that classifies pancreatic intraductal neoplasms into <jats:styled-content style=\"fixed-case\">IPMN<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">ITPN<\/jats:styled-content> and confirm that <jats:styled-content style=\"fixed-case\">IPMN\u2010PG<\/jats:styled-content> is not a benign counterpart of <jats:styled-content style=\"fixed-case\">ITPN<\/jats:styled-content>. The term \u2018intraductal tubular adenoma\u2019 should be eliminated and replaced with <jats:styled-content style=\"fixed-case\">IPMN\u2010PG<\/jats:styled-content>. Copyright \u00a9 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley &amp; Sons, Ltd.<\/jats:bold><\/jats:p>","DOI":"10.1002\/path.4242","type":"journal-article","created":{"date-parts":[[2013,7,25]],"date-time":"2013-07-25T15:12:59Z","timestamp":1374765179000},"page":"335-341","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":62,"title":["The discrete nature and distinguishing molecular features of pancreatic intraductal tubulopapillary neoplasms and intraductal papillary mucinous neoplasms of the gastric type, pyloric gland variant"],"prefix":"10.1002","volume":"231","author":[{"given":"Hiroshi","family":"Yamaguchi","sequence":"first","affiliation":[{"name":"Institute for Integrated Medical Sciences Tokyo Women's Medical University Tokyo Japan"},{"name":"Department of Pathology Saitama International Medical Center, Saitama Medical University Hidaka 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