TY - JOUR
T1 - Direct correlation between proliferative activity and dysplasia in pancreatic intraepithelial neoplasia (panIN)
T2 - Additional evidence for a recently proposed model of progression
AU - Klein, Walter M.
AU - Hruban, Ralph H.
AU - Klein-Szanto, Andres J.P.
AU - Wilentz, Robb E.
PY - 2002
Y1 - 2002
N2 - 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.
AB - 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.
KW - Ki-67 pancreas
KW - PanIN
KW - Pancreatic intraepithelial neoplasia
KW - Proliferation
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U2 - 10.1038/modpathol.3880544
DO - 10.1038/modpathol.3880544
M3 - Article
C2 - 11950919
AN - SCOPUS:0036230171
VL - 15
SP - 441
EP - 447
JO - Modern Pathology
JF - Modern Pathology
SN - 0893-3952
IS - 4
ER -