title: Pancreatic intraepithelial neoplasia and pancreatic tumorigenesis: of mice and men.
abstract: BACKGROUND
  Pancreatic cancer has a poor prognosis with a 5-year survival of less than 5%. Early detection is at present the only way to improve this outlook. This review focuses on the recent advances in our understanding of pancreatic carcinogenesis, the scientific evidence for a multistaged tumor progression, and the role genetically engineered mouse models can play in recapitulating the natural course and biology of human disease.
  
  
  OBJECTIVE
  To illustrate the stepwise tumor progression of pancreatic cancer and genetic alterations within the different stages of progression and to review the findings made with genetically engineered mouse models concerning pancreatic carcinogenesis.
  
  
  METHODS
  A review of recent literature on pancreatic tumorigenesis and genetically engineered mouse models.
  
  
  CONCLUSIONS
  Pancreatic cancer develops through stepwise tumor progression in which preinvasive stages, called pancreatic intraepithelial neoplasia, precede invasive pancreatic cancer. Genetic alterations in oncogenes and tumor suppressor genes underlying pancreatic cancer are also found in pancreatic intraepithelial neoplasia. These mutations accumulate during progression through the consecutive stages of pancreatic intraepithelial neoplasia lesions. Also in genetically engineered mouse models of pancreatic ductal adenocarcinoma, tumorigenesis occurs through stepwise progression via consecutive mouse pancreatic intraepithelial neoplasia, and these models provide important tools for clinical applications. Nevertheless differences between mice and men still remain.
authors.affiliation: Department of Pathology, University Medical Center, Utrecht, the Netherlands.
authors.forename: Niki A
authors.initials: NA
authors.lastname: Ottenhof
authors.forename: Anya N A
authors.initials: AN
authors.lastname: Milne
authors.forename: Folkert H M
authors.initials: FH
authors.lastname: Morsink
authors.forename: Paul
authors.initials: P
authors.lastname: Drillenburg
authors.forename: Fiebo J W
authors.initials: FJ
authors.lastname: Ten Kate
authors.forename: Anirban
authors.initials: A
authors.lastname: Maitra
authors.forename: G Johan
authors.initials: GJ
authors.lastname: Offerhaus
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis / Q000235:genetics*; D000818:Animals; D002278:Carcinoma in Situ / Q000175:diagnosis / Q000235:genetics*; D004195:Disease Models, Animal; D018450:Disease Progression; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D010190:Pancreatic Neoplasms / Q000175:diagnosis / Q000235:genetics*; D011379:Prognosis