[1776] Characterization of Putative Precursor Lesions of Familial Pancreatic Cancer

Bjorn Konukiewitz, Anna Melissa Schlitter, Sonja Berchtold, Susanne Haneder, Peter Langer, Detlef Bartsch, Gunter Kloppel, Irene Esposito. Technical University of Munich, Munich, Germany; University of Gießen and Marburg, Marburg, Germany

Background: The well characterized precursor lesions of pancreatic ductal adenocarcinoma (PDAC) such as PanIN, IPMN and MCN show a ductal phenotype. However, acinar cells might also be involved in PDAC origin, since genetically engineered mouse models revealed that pancreatic carcinomas may arise from atypical flat lesions (AFL) which derive from tubular cell complexes (TC) in areas of acinar-ductal metaplasia (ADM). Human AFL have also been detected in areas of ADM in pancreata from individuals with a history of familial pancreatic cancer (FPC). In this study, we analyzed pancreas resection specimens from FPC individuals in order to search for PDAC precursor lesions and analyze their phenotype. In particular, we looked for AFL as indication for a PanIN-independent carcinogenic pathway.
Design: We systematically screened pancreatic specimens, removed from six healthy individuals with a FPC history, for ductal and acinar lesions such as PanIN, IPMN, TC and AFL. Immunostaining for MUC1, MUC2, MUC5, MUC6, p53, smad4 and Her2neu and MIB1 as well as K-RAS mutation analysis was performed on all identified lesions.
Results: In addition to precursor lesions of ductal phenotype such as PanIN (many with lobulocentric fibrosis) and gastric type IPMN, all pancreata also showed AFLs in ADM areas that displayed a perifocal active stromal reaction. AFL showed predominantly a MUC1+, MUC2- and MUC5+ expression pattern with a variable positivity for MUC6 and a focally elevated Ki-67 proliferation index. AFL from 2 cases also harbored mutations in the K-RAS-gene locus.
Conclusions: Pancreatic tissue from FPC individuals not only contain PanINs and IPMNs but also AFLs. The identification of the latter lesions suggests a potentially alternative pathway of carcinogenesis in FPC, that starts in ADM areas. Whether AFLs also play a role in the development of sporadic PDAC is not yet known.
Category: Pancreas

Tuesday, March 5, 2013 2:15 PM

Proffered Papers: Section F, Tuesday Afternoon

 

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