Morphogenesis of pancreatic cancer: role of pancreatic intraepithelial neoplasia (PanINs)

Langenbecks Arch Surg. 2008 Jul;393(4):561-70. doi: 10.1007/s00423-008-0282-x. Epub 2008 Feb 19.


Introduction: Pancreatic ductal adenocarcinoma (i.e., pancreatic cancer) is an almost universally lethal disease. The identification of precursor lesions of pancreatic cancer provides an opportunity for early detection and potential therapeutic intervention before the development of invasive cancer.

Discussion: It is now established that pancreatic cancers do not arise de novo but rather exhibit a sequential histological and genetic progression of precursor lesions culminating in frank, invasive neoplasia. Pancreatic intraepithelial neoplasia (PanIN) is the most common non-invasive precursor lesion of pancreatic cancer. The development of a consensus nomenclature scheme for PanINs has facilitated research into pancreatic cancer precursors and enabled standardization of results across institutions.

Conclusion: PanINs harbor many of the molecular alterations observed in invasive pancreatic cancer, confirming their status as true non-invasive precursor lesions. Recently developed genetically engineered mouse models of pancreatic cancer also demonstrate the stepwise PanIN progression model, underscoring the commonalities in pancreatic neoplasia between mouse and man.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Animals
  • Carcinoma in Situ / genetics
  • Carcinoma in Situ / pathology*
  • Carcinoma, Pancreatic Ductal / genetics
  • Carcinoma, Pancreatic Ductal / pathology*
  • Cell Transformation, Neoplastic / genetics
  • Cell Transformation, Neoplastic / pathology*
  • DNA Damage / genetics
  • DNA Mutational Analysis
  • DNA Repair / genetics
  • Disease Models, Animal
  • Epigenesis, Genetic / genetics
  • Gastric Mucins / genetics
  • Gene Expression Regulation, Neoplastic
  • Genes, Suppressor
  • Genetic Engineering
  • Humans
  • Mice
  • MutL Protein Homolog 1
  • MutS Homolog 2 Protein / genetics
  • Nuclear Proteins / genetics
  • Pancreas / pathology
  • Pancreatic Neoplasms / genetics
  • Pancreatic Neoplasms / pathology*
  • Precancerous Conditions / genetics
  • Precancerous Conditions / pathology*
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins p21(ras)
  • Signal Transduction / genetics
  • ras Proteins / genetics


  • Adaptor Proteins, Signal Transducing
  • Gastric Mucins
  • KRAS protein, human
  • MLH1 protein, human
  • Nuclear Proteins
  • Proto-Oncogene Proteins
  • apomucin
  • MSH2 protein, human
  • MutL Protein Homolog 1
  • MutS Homolog 2 Protein
  • Proto-Oncogene Proteins p21(ras)
  • ras Proteins