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Aichler, M. ; Seiler, C.* ; Tost, M. ; Siveke, J.* ; Mazur, P.K.* ; Da Silva-Buttkus, P. ; Bartsch, D.K.* ; Langer, P.* ; Chiblak, S.* ; Dürr, A.* ; Höfler, H.* ; Klöppel, G.* ; Müller-Decker, K.* ; Brielmeier, M. ; Esposito, I.

Origin of pancreatic ductal adenocarcinoma from atypical flat lesions: A comparative study in transgenic mice and human tissues.

J. Pathol. 226, 723-734 (2012)
Postprint DOI PMC
Open Access Green
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 kras under the control of a pancreas-specific promoter that ductal cancer might arise in the centroacinar-acinar region, possibly through a process of acinar-ductal 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 was performed in the Kras(G12D/+) ;Ptf1a-Cre(ex1/+) 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 Kras(G12D/+) ;Ptf1a-cre(ex1/+) 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 Kras(G12D/+) ;Ptf1a-Cre(ex1/+) mice starts from ADM and a similar process might also take place in patients with a strong family history of PDAC.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter familial pancreatic cancer; PanIN; tubular complexes; precursor lesions; mouse model; Kras
ISSN (print) / ISBN 0022-3417
e-ISSN 1096-9896
Zeitschrift Journal of Pathology, The
Quellenangaben Band: 226, Heft: 5, Seiten: 723-734 Artikelnummer: , Supplement: ,
Verlag Wiley
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Research Unit Analytical Pathology (AAP)
Institute of Pathology (PATH)
CF Comparative Medicine (CF-Comparative Medicine)