Frequency of K-ras Mutations in Pancreatic Intraductal Neoplasias Associated with Pancreatic Ductal Adenocarcinoma and Chronic Pancreatitis: A Meta-Analysis
Molecular analyses have demonstrated mutations in the K-ras gene at codon 12 in the majority of pancreatic ductal adenocarcinomas (PDACs). In order to determine whether the K-ras mutation rate increases parallel to the grade of dysplasia in duct lesions, we performed a meta-analysis of the studies...
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doaj-d9b1f473d7f54c1ba4291293e9ebda492020-11-24T22:32:54ZengElsevierNeoplasia: An International Journal for Oncology Research1476-55861522-80022005-01-0171172310.1593/neo.04445Frequency of K-ras Mutations in Pancreatic Intraductal Neoplasias Associated with Pancreatic Ductal Adenocarcinoma and Chronic Pancreatitis: A Meta-AnalysisMatthias Löhr0Gunter Klöppel1Patrick Maisonneuve2Albert B. Lowenfels3Jutta Lüttges4Department of Medicine II, Medical Faculty Mannheim, University of Heidelberg, Heidelberg, GermanyDepartment of Pathology, University of Kiel, Kiel, GermanyDivision of Epidemiology and Biostatistics, European Institute of Oncology, Milan, ItalyDivision of Epidemiology and Biostatistics, European Institute of Oncology, Milan, ItalyDepartment of Pathology, University of Kiel, Kiel, Germany Molecular analyses have demonstrated mutations in the K-ras gene at codon 12 in the majority of pancreatic ductal adenocarcinomas (PDACs). In order to determine whether the K-ras mutation rate increases parallel to the grade of dysplasia in duct lesions, we performed a meta-analysis of the studies published between 1988 and 2003 that provide information on K-ras mutations in hyperplastic and dysplastic duct lesions in the pancreas. The described duct lesions were reclassified according to the nomenclature for pancreatic intraepithelial neoplasia (PanIN), and the molecular methods for detecting K-ras were reviewed. In PanIN lesions from pancreata of patients with PDAC, there was a stepwise increase in K-ras mutations that correlated with the grade of dysplasia of the PanIN lesion. K-ras mutations were found in 36%, 44%, and 87% of PanIN-1a, 1b, and 2–3 lesions, respectively (trend statistic P<.001). Mutation-enriched polymerase chain reaction (PCR) resulted in higher rates of K-ras mutations in PanIN than plain PCR did. The incidence of K-ras mutations in PanIN lesions associated with chronic pancreatitis (CP) or normal pancreas was low (around 10%). In CP, K-ras mutations were only found after a disease duration of 3 years. The correlation of the incidence of K-ras mutations with the grade of dysplasia in PanIN and the occurrence of these mutations in CP with a duration of more than 3 years underlines the importance of this genetic change for the development of PDAC. http://www.sciencedirect.com/science/article/pii/S1476558605800958K-ras mutationpancreatic ductal carcinomachronic pancreatitispancreatic intraepithelial neoplasiameta-analysis |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Matthias Löhr Gunter Klöppel Patrick Maisonneuve Albert B. Lowenfels Jutta Lüttges |
spellingShingle |
Matthias Löhr Gunter Klöppel Patrick Maisonneuve Albert B. Lowenfels Jutta Lüttges Frequency of K-ras Mutations in Pancreatic Intraductal Neoplasias Associated with Pancreatic Ductal Adenocarcinoma and Chronic Pancreatitis: A Meta-Analysis Neoplasia: An International Journal for Oncology Research K-ras mutation pancreatic ductal carcinoma chronic pancreatitis pancreatic intraepithelial neoplasia meta-analysis |
author_facet |
Matthias Löhr Gunter Klöppel Patrick Maisonneuve Albert B. Lowenfels Jutta Lüttges |
author_sort |
Matthias Löhr |
title |
Frequency of K-ras Mutations in Pancreatic Intraductal Neoplasias Associated with Pancreatic Ductal Adenocarcinoma and Chronic Pancreatitis: A Meta-Analysis |
title_short |
Frequency of K-ras Mutations in Pancreatic Intraductal Neoplasias Associated with Pancreatic Ductal Adenocarcinoma and Chronic Pancreatitis: A Meta-Analysis |
title_full |
Frequency of K-ras Mutations in Pancreatic Intraductal Neoplasias Associated with Pancreatic Ductal Adenocarcinoma and Chronic Pancreatitis: A Meta-Analysis |
title_fullStr |
Frequency of K-ras Mutations in Pancreatic Intraductal Neoplasias Associated with Pancreatic Ductal Adenocarcinoma and Chronic Pancreatitis: A Meta-Analysis |
title_full_unstemmed |
Frequency of K-ras Mutations in Pancreatic Intraductal Neoplasias Associated with Pancreatic Ductal Adenocarcinoma and Chronic Pancreatitis: A Meta-Analysis |
title_sort |
frequency of k-ras mutations in pancreatic intraductal neoplasias associated with pancreatic ductal adenocarcinoma and chronic pancreatitis: a meta-analysis |
publisher |
Elsevier |
series |
Neoplasia: An International Journal for Oncology Research |
issn |
1476-5586 1522-8002 |
publishDate |
2005-01-01 |
description |
Molecular analyses have demonstrated mutations in the K-ras gene at codon 12 in the majority of pancreatic ductal adenocarcinomas (PDACs). In order to determine whether the K-ras mutation rate increases parallel to the grade of dysplasia in duct lesions, we performed a meta-analysis of the studies published between 1988 and 2003 that provide information on K-ras mutations in hyperplastic and dysplastic duct lesions in the pancreas. The described duct lesions were reclassified according to the nomenclature for pancreatic intraepithelial neoplasia (PanIN), and the molecular methods for detecting K-ras were reviewed. In PanIN lesions from pancreata of patients with PDAC, there was a stepwise increase in K-ras mutations that correlated with the grade of dysplasia of the PanIN lesion. K-ras mutations were found in 36%, 44%, and 87% of PanIN-1a, 1b, and 2–3 lesions, respectively (trend statistic P<.001). Mutation-enriched polymerase chain reaction (PCR) resulted in higher rates of K-ras mutations in PanIN than plain PCR did. The incidence of K-ras mutations in PanIN lesions associated with chronic pancreatitis (CP) or normal pancreas was low (around 10%). In CP, K-ras mutations were only found after a disease duration of 3 years. The correlation of the incidence of K-ras mutations with the grade of dysplasia in PanIN and the occurrence of these mutations in CP with a duration of more than 3 years underlines the importance of this genetic change for the development of PDAC.
|
topic |
K-ras mutation pancreatic ductal carcinoma chronic pancreatitis pancreatic intraepithelial neoplasia meta-analysis |
url |
http://www.sciencedirect.com/science/article/pii/S1476558605800958 |
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