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

Abstract

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.

Fig. 1

A “PanINgram” illustrating some of the molecular alterations that occur during the multi-step progression of pancreatic adenocarcinomas. The molecular abnormalities listed are not comprehensive, and additional alterations are discussed in the text at the appropriate juncture. Adapted from [45]