Medline ® Abstract for Reference 16
of 'Molecular pathogenesis of exocrine pancreatic cancer'
Prevalence of activating K-ras mutations in the evolutionary stages of neoplasia in intraductal papillary mucinous tumors of the pancreas.
Z'graggen K, Rivera JA, Compton CC, Pins M, Werner J, Fernández-del Castillo C, Rattner DW, Lewandrowski KB, Rustgi AK, Warshaw AL
Ann Surg. 1997;226(4):491.
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.
Department of Surgery, Massachusetts General Hospital and Harvard Medical School, Boston 02114, USA.