Proliferative activity in pancreatic intraepithelial neoplasias of chronic pancreatitis resection specimens: detection of a high-risk lesion

Abstract

Patients with chronic pancreatitis have a markedly increased risk of pancreatic cancer compared with general population. Mechanism of the increased risk is not completely known. The current progression model for pancreatic ductal adenocarcinoma proposes the progression from normal ductal epithelium through a series of lesions called pancreatic intraepithelial neoplasias (PanINs) to invasive cancer. These lesions are frequently seen in chronic pancreatitis tissue. Proliferative activity in PanINs of chronic pancreatitis tissue has not been separately studied using the current nomenclature. Our study included 36 chronic pancreatitis resection specimens. A total number of 106 PanINs found within 32 resection specimens was histologically graded and then immunolabeled using a monoclonal antibody against Ki-67 that is expressed in dividing cells. The Ki-67 labeling indices in the increasing grades of PanINs were counted with following results: PanIN-1A, 0.77%; PanIN-1B, 3.26%; PanIN-2, 14.68%; and PanIN-3, 25.4%. The difference in Ki-67 labeling indices among these types of lesions was statistically significant (p<0.001, t-test). These results correlate with known genetic alterations found in chronic pancreatitis, especially with p16 inactivation that was recently described in PanINs arising in patients with chronic pancreatitis. Moreover, our findings support the currently accepted pancreatic progression model and Ki-67 immunohistochemistry might represent an efficient tool for an identification of a high-risk lesion.