{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T05:10:03Z","timestamp":1790485803045,"version":"4.1.0"},"reference-count":33,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2012,1,17]],"date-time":"2012-01-17T00:00:00Z","timestamp":1326758400000},"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":[[2012,4]]},"abstract":"Abstract<\/jats:title>\n \n Pancreatic ductal adenocarcinoma (PDAC) and its precursor lesions, pancreatic intraepithelial neoplasia (PanIN), display a ductal phenotype. However, there is evidence in genetically defined mouse models for PDAC harbouring a mutated\n kras<\/jats:italic>\n under the control of a pancreas\u2010specific promoter that ductal cancer might arise in the centroacinar\u2010acinar region, possibly through a process of acinar\u2010ductal metaplasia (ADM). In order to further elucidate this model of PDAC development, an extensive expression analysis and molecular characterization of the putative and already established (PanIN) precursor lesions were performed in the\n Kras<\/jats:italic>\n \n $^{G{\\it{\\bf{12}}}D\/+}$\n \n <\/jats:styled-content>\n ; Ptf1a\u2010Cre<\/jats:italic>\n \n $^{ex{\\it{\\bf{1}}}\/+}$\n \n <\/jats:styled-content>\n mouse model and in human tissues, focusing on lineage markers, developmental pathways, cell cycle regulators, apomucins, and stromal activation markers. The results of this study show that areas of ADM are very frequent in the murine and human pancreas and represent regions of increased proliferation of cells with precursor potential. Moreover, atypical flat lesions originating in areas of ADM are the most probable precursors of PDAC in the\n Kras<\/jats:italic>\n \n $^{G{\\it{\\bf{12}}}D\/+}$\n \n <\/jats:styled-content>\n ; Ptf1a\u2010Cre<\/jats:italic>\n \n $^{ex{\\it{\\bf{1}}}\/+}$\n \n <\/jats:styled-content>\n mice and similar lesions were also found in the pancreas of three patients with a strong family history of PDAC. In conclusion, PDAC development in\n Kras<\/jats:italic>\n \n $^{G{\\it{\\bf{12}}}D\/+}$\n \n <\/jats:styled-content>\n ; Ptf1a\u2010Cre<\/jats:italic>\n \n $^{ex{\\it{\\bf{1}}}\/+}$\n \n <\/jats:styled-content>\n mice starts from ADM and a similar process might also take place in patients with a strong family history of PDAC. Copyright \u00a9 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.\n <\/jats:p>","DOI":"10.1002\/path.3017","type":"journal-article","created":{"date-parts":[[2011,10,7]],"date-time":"2011-10-07T17:05:19Z","timestamp":1318007119000},"page":"723-734","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":124,"title":["Origin of pancreatic ductal adenocarcinoma from atypical flat lesions: a comparative study in transgenic mice and human 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