Pancreatic Intraepithelial Neoplasia Revisited and Updated

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Abstract

Most pancreatic neoplasms are classified as ductal adenocarcinoma because they show a ductal phenotype, making a ductal origin very likely. The duct lesions that may give rise to pancreatic ductal adenocarcinoma have been called pancreatic intraepithelial neoplasia (PanIN). A classification system for these lesions distinguishes between three grades of PanIN. Molecular studies revealed that PanIN-2 and PanIN-3 lesions represent a distinct step towards invasive carcinoma. While high-grade PanINs are extremely rare in the normal pancreas, low-grade PanINs are common in individuals older than 40 years and may be associated with lobular fibrosis and intraductal papillary mucinous neoplasms of the gastric type. This disease spectrum has also been described in members of kindreds with familial pancreatic cancer. The natural history and cause of PanINs are unknown. As PanIN-1 lesions entail little risk, while PanIN-3 lesions are high-risk lesions, it would be of interest to target PanIN-2 lesions, which can be regarded as the starting point of progressive neoplastic changes that lead to invasive pancreatic ductal adenocarcinoma. Global gene expression analysis identified several differentially expressed genes which show enhanced expression in PanINs and may be used as potential biomarkers to facilitate diagnosis and therapy.

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      Oncogenic KRAS activates the MAP (Mitogen Activate Protein) kinase and the PI3 (Phosphoinositide 3) kinase pathways, leading to an increased proliferation. KRAS mutation is considered as an early event during pancreatic carcinogenesis occurring in 35% of low grade PanINs and reaching 75% in high grade PanINs [10]. This mutation facilitates the progression from low grade to high grade PanINs and is sufficient to initiate the PanIN lesions.

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    PD Dr. Bence Sipos Department of Pathology, University of Kiel Michaelisstrasse 11 DE-24105 Kiel (Germany) Tel. +49 431 597 3402, Fax +49 431 597 3462

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