title: Direct correlation between proliferative activity and dysplasia in pancreatic intraepithelial neoplasia (PanIN): additional evidence for a recently proposed model of progression.
abstract: A growing body of morphological, clinical, and genetic observations suggests a progression model for pancreatic ductal adenocarcinoma. In this model, pancreatic ducts progress through a series of architectural and cytological changes that define degrees of pancreatic intraepithelial neoplasia (PanIN). Expressed in dividing cells, Ki-67 has been extensively used as a proliferation marker. Its expression in different grades of PanIN has not been well studied. A total of 76 PanINs from 41 patients were histologically graded according to recently established criteria. These PanINs were then immunolabeled with a monoclonal antibody against Ki-67 (Mib-1). Normal ducts and invasive ductal adenocarcinomas were also labeled with the antibody. In 15 normal ducts, only 0.41% of the epithelial cells expressed Ki-67. Ki-67-labeling indices in the increasing grades of PanIN were as follows: PanIN-1A, 0.69%; PanIN-1B, 2.33%; PanIN-2, 14.08%; and PanIN-3, 22.01%. Fifteen invasive ductal adenonocarcinomas showed an average labeling index of 36.99%. The difference in Ki-67 labeling among these groups was statistically significant (P <.0005, Kruskal-Wallis test). This pattern of proliferation provides additional evidence supporting the recently proposed pancreatic progression model. It also correlates well with known molecular changes, such as activating point mutations in the K-ras oncogene and the loss of DPC4 and p16 gene expression. Ki-67 staining may be useful as an adjunct in the diagnosis of precancerous lesions in the pancreas and may provide a reliable way to identify lesions at high risk for the subsequent development of infiltrating carcinoma.
authors.affiliation: Department of Pathology, The Johns Hopkins Medical Institutions, Baltimore, Maryland 21205, USA.
authors.forename: Walter M
authors.initials: WM
authors.lastname: Klein
authors.forename: Ralph H
authors.initials: RH
authors.lastname: Hruban
authors.forename: Andres J P
authors.initials: AJ
authors.lastname: Klein-Szanto
authors.forename: Robb E
authors.initials: RE
authors.lastname: Wilentz
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology; D018450:Disease Progression; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000032:analysis*; D008954:Models, Biological; D010183:Pancreatic Ducts / Q000737:chemistry / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000378:metabolism / Q000473:pathology*
chemical_list: D019394:Ki-67 Antigen