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Pancreatic Carcinogenesis

  • V. TaucherEmail author
  • Johannes Haybaeck
Chapter
  • 572 Downloads

Abstract

Pancreatic cancer (PC) is a lethal disease with a devastating prognosis. This is due to the late occurrence of clinical symptoms in advanced cases, where operative cure is seldom possible. PC is divided into subtypes, which include pancreatic ductal adenocarcinoma (PDAC), colloid carcinoma (CC), pancreatoblastoma, cystadenocarcinoma, and histologically-mixed types. PDAC is the most common and aggressive subtype, comprising 95% of PC cases. It evolves by a series of molecular aberrations that lead to malignant transformation. The precursor lesions pancreatic intraepithelial neoplasia (PanIN), intraductal papillary mucinous neoplasm (IPMN), and mucinous cystic neoplasm (MCN) can evolve into PDAC. In most cases, however, PanINs are the precursors of PDAC. IPMN progresses to either PDAC or CC, depending on the histologic subtype of the underlying IMPN. The microscopically visible PanINs are well characterized molecularly and genetically, which has helped in determining the sequence of changes that occur during pancreatic carcinogenesis. IPMNs and MCNs are macroscopic lesions that are seen with standard imaging techniques and often present with a cystic morphology and symptoms attributable to ductal obstruction. Activating KRAS mutations are the most common mutation in PanINs and IPMNs. Studies have shown that constitutively active KRAS leads to changes that involve not only increased growth of tumor cells but also gives precursor lesions a survival advantage by promoting tumor desmoplasia, anabolic metabolism, and immunologic tumor tolerance. Furthermore, the occurrence of TP53 mutations in PanINs with mutant KRAS has been shown to be essential for the transformation to PDAC. Multiple pathways are altered in pancreatic carcinogenesis. These include MAPK/ERK, PI3K/AKT, Wnt/β-catenin, TGF-β, hedgehog, chromatin regulation, autophagy, and G1/S-phase transition. Moreover, noncoding RNA has been shown to be involved in almost all steps of pancreatic carcinogenesis.

Keywords

Adenomatous Polyposis Coli KRAS Mutation TP53 Mutation Intraductal Papillary Mucinous Neoplasm Ataxia Telangiectasia Mutate 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer International Publishing AG 2017

Authors and Affiliations

  1. 1.Institute of Pathology, Medical University of GrazGrazAustria
  2. 2.Department of Pathology, Medical FacultyOtto von Guericke University MagdeburgMagdeburgGermany
  3. 3.Institute of PathologyMedical University of GrazGrazAustria

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