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

Kaspar Z'graggen, Jaime A. Rivera, Carolyn C. Compton, Michael Pins, Jens Werner, Carlos Fernández-del Castillo, David W. Rattner, Kent B. Lewandrowski, Anil K. Rustgi, Andrew L. Warshaw

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187 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)491-500
Number of pages10
JournalAnnals of Surgery
Volume226
Issue number4
DOIs
StatePublished - 1997

ASJC Scopus subject areas

  • Surgery

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    Z'graggen, K., Rivera, J. A., Compton, C. C., Pins, M., Werner, J., Fernández-del Castillo, C., Rattner, D. W., Lewandrowski, K. B., Rustgi, A. K., & Warshaw, A. L. (1997). Prevalence of activating K-ras mutations in the evolutionary stages of neoplasia in intraductal papillary mucinous tumors of the pancreas. Annals of Surgery, 226(4), 491-500. https://doi.org/10.1097/00000658-199710000-00010