Pancreatic cancer is the fifth leading cause of cancer death in the USA. Unfortunately, there is currently no effective screening test for asymptomatic disease and the vast majority of patients with pancreatic cancer present with advanced incurable disease. An effective method to detect early pancreatic cancers is urgently needed. This need is perhaps greatest in groups known to have an increased risk of developing pancreatic cancer. For example, patients with sporadic chronic pancreatitis have a lifetime risk of developing pancreatic cancer that approaches 4% and for patients with hereditary pancreatitis, the lifetime risk of pancreatic cancer is very high (approximately 50%). An improved understanding of early neoplasia in patients with chronic pancreatitis should form the foundation on which novel approaches to the early identification of invasive cancer could be developed. Several lines of evidence suggests that the precursor lesions of pancreatic carcinoma are the duct lesions known as pancreatic intraepithelial neoplasias (PanINs). First, PanINs are more common in pancreata with cancer than they were in pancreata without cancer. Second, PanINs found in pancreata with pancreatic cancer harbor many of the same genetic alterations as are found in pancreatic cancer such as activation of K-ras and inactivation of p16, DPC4, p53, and BRCA2. Third, several case studies report patients with PanINs progressing to invasive pancreatic cancer. Despite the risk of pancreatic cancer among patients with chronic pancreatitis, the genetic alterations in the PanINs from patients with chronic pancreatitis have not been well-studied.
The aim of this study is to compare the frequency, timing and mechanism of several molecular events important for neoplastic progression in PanINs found in the setting of pancreatic cancer with PanINs found in the setting of chronic pancreatitis- associated and with PanINs from other benign pancreatic conditions. Specifically, using genetic, DNA methylation, and immunohistochemical techniques to compare the rates of a) genetic inactivation of DPC4 and b) genetic and epigenetic inactivation of p16 in 40 PanINs that arose in the setting of chronic pancreatitis 40 PanINs that arose in the setting of pancreatic cancer and 40 PanINs that arose in pancreata resected for benign pancreatic conditions without malignant potential.
