Prevalence of activating K-ras mutations in the evolutionary stages of neoplasia in intraductal papillary mucinous tumors of the pancreas

被引:169
|
作者
Zgraggen, K
Rivera, JA
Compton, CC
Pins, M
Werner, J
FernandezdelCastillo, C
Rattner, DW
Lewandrowski, KB
Rustgi, AK
Warshaw, AL
机构
[1] MASSACHUSETTS GEN HOSP,DEPT SURG,BOSTON,MA 02114
[2] MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114
[3] MASSACHUSETTS GEN HOSP,GASTROINTESTINAL UNIT,BOSTON,MA 02114
[4] HARVARD UNIV,SCH MED,BOSTON,MA
关键词
D O I
10.1097/00000658-199710000-00010
中图分类号
R61 [外科手术学];
学科分类号
摘要
Objective The purpose of the study was to determine the prevalence of activating K-ras mutations in the pancreas of patients with intraductal papillary mucinous tumors (IPMT) and to analyze their relation to the degree of site-specific histopathologic abnormality. Background Intraductal papillary mucinous tumors of the pancreas have a biologic behavior that is significantly different from pancreatic ductal adenocarcinoma. Activating K-ras mutations, which may be important events in a multistage process of carcinogenesis, have been reported in IPMT. Methods Forty-six different histologic specimens (comprising normal pancreatic ducts, hyperplasia, low-grade dysplasia, high-grade dysplasia-carcinoma in situ, and carcinoma) from 16 patients with IPMT and 9 specimens from patients with pancreatic ductal adenocarcinomas were designated by a pathologist. Genomic DNA was extracted from paraffin-embedded tissue sections after microdissection. The K-ras gene was amplified by polymerase chain reaction and subjected to DNA sequencing. Results The K-ras mutations were detected in at least one specimen in 13 (81.2%) of 16 patients with IPMT. All mutations were found in codon 12. No codon 13 mutations were detected. The relative frequency of K-ras mutations in the different stages of IPMT was 16.7% in normal epithelium and papillary hyperplasia, 28.6% in low-grade dysplasia, and 57.1% in high-grade dysplasia-carcinoma in situ and invasive carcinoma. The K-ras mutations were detected in 6 (66%) of 9 pancreatic ductal adenocarcinomas. Conclusions The K-ras codon 12 point mutations are as frequent in IPMT as in ductal adenocarcinoma. A stepwise increase in the frequency of codon 12 mutations correlated with the stage of neoplastic evolution to cancer. This finding is consistent with an important role of K-ras gene mutations in the transformation from normal epithelium to invasive carcinoma in the majority of patients with IPMT.
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页码:491 / 498
页数:8
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