The K-ras mutation pattern in pancreatic ductal adenocarcinoma usually is identical to that in associated normal, hyperplastic, and metaplastic ductal epithelium

Cancer. 1999 Apr 15;85(8):1703-10.


Background: Hyperplastic ductal lesions of the pancreas are believed to represent precursors of ductal adenocarcinoma. The most frequent mutation in manifest ductal carcinoma of the pancreas is the K-ras mutation at codon 12. The frequency and significance of this mutation in precursor lesions are a matter of controversy.

Methods: The study included 35 resection specimens of ductal adenocarcinoma of the head of the pancreas and 3 noncancerous, noninflammatory pancreases. Ductal lesions were classified according to established criteria. Single cells from these lesions were microdissected and analyzed by the denaturing gradient gel electrophoresis polymerase chain reaction method.

Results: All primary adenocarcinomas showed a K-ras mutation at codon 12 (25 cases with GAT, 7 cases with GTT, and 3 cases with CGT). One hundred and six of 364 ductal lesions were positive for the mutation. The highest relative percentage (53%) occurred in adenomatoid hyperplasia, followed by 36% in papillary hyperplasia, 26% in mucinous hypertrophy, and 14% in squamous metaplasia. With only two exceptions the mutation pattern of the ductal lesions and that of the corresponding primary tumor were identical. Twenty-one samples from normal ducts (17%) also harbored the K-ras mutation, as did 3 lesions from noncancerous specimens.

Conclusions: K-ras mutations are common events in normal, hyperplastic, metaplastic, and neoplastic pancreatic ductal cells. Because K-ras mutations frequently, although not exclusively, are related to mucinous differentiation of pancreatic cells, this mutation may not cause but only promote mucinous differentiation. The prevalence of a certain mutation pattern in nonneoplastic and neoplastic ductal cells in an individual pancreas suggests the dominance of one carcinogenic factor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / chemistry
  • Adenocarcinoma / genetics*
  • Adenocarcinoma, Mucinous / genetics
  • Adenocarcinoma, Mucinous / metabolism
  • Adenocarcinoma, Mucinous / pathology
  • Aged
  • Codon / genetics*
  • DNA Mutational Analysis
  • DNA, Neoplasm / genetics
  • Epithelial Cells / chemistry
  • Genes, ras*
  • Humans
  • Hyperplasia
  • Metaplasia
  • Middle Aged
  • Neoplasm Proteins / genetics*
  • Pancreatic Diseases / genetics*
  • Pancreatic Diseases / metabolism
  • Pancreatic Diseases / pathology
  • Pancreatic Ducts / chemistry*
  • Pancreatic Ducts / pathology
  • Pancreatic Neoplasms / chemistry
  • Pancreatic Neoplasms / genetics*
  • Point Mutation*
  • Precancerous Conditions / genetics*
  • Precancerous Conditions / metabolism
  • Precancerous Conditions / pathology
  • Proto-Oncogene Proteins p21(ras) / genetics


  • Codon
  • DNA, Neoplasm
  • Neoplasm Proteins
  • HRAS protein, human
  • Proto-Oncogene Proteins p21(ras)