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BACKGROUND : Pancreatic adenocarcinoma is a relatively frequent cancer with an extremely poor prognosis. Until recently, the natural history of pancreatic adenocarcinoma has not been possible to study, but the identification of precursor lesions (pancreatic intraepithelial neoplasia, PanIN) has lead to a better understanding of the stepwise morphological and genetic alterations involved in the development of invasive adenocarcinoma. MATERIAL AND METHODS : Relevant literature from the period of 1996-2005 was found by searching the Medline database, combining the terms "pancreas", "cancer", "PanIN" and "neoplasia". Principal original and review papers were extracted and used as background for a presentation of the PanIN cancer progression model. RESULTS AND INTERPRETATION : PanINs are established as designation of histological precursor lesions to pancreatic adenocarcinoma. PanIN grade I to III represent stepwise morphological alterations in the pancreatic ductal epithelium, from early neoplasia (PanIN I and II), via carcinoma in situ (PanIN III) to the development of invasive ductal adenocarcinoma. This model allows for the investigation of sequential molecular changes such as activation of oncogenes and inactivation of tumour suppressor genes. Increased knowledge about pancreatic carcinogenesis may pave the way for prevention strategies, early detection, and new treatment options, thus ultimately improving the prognosis of the patients.

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