Frequent and significant K-ras mutation in the pancreas, the bile duct, and the gallbladder in autoimmune pancreatitis

Pancreas. 2009 Nov;38(8):890-5. doi: 10.1097/MPA.0b013e3181b65a1c.

Abstract

Objectives: To assess the relationship between autoimmune pancreatitis (AIP) and pancreatic cancer, we analyzed K-ras mutation in the pancreatobiliary tissues of patients with AIP.

Methods: An analysis of K-ras mutation and an immunohistochemical study were performed on the pancreas of 8 patients with AIP and 10 patients with chronic alcoholic pancreatitis and on the common bile duct and the gallbladder of 9 patients with AIP. K-ras mutation was analyzed in the pure pancreatic juice from 3 patients with AIP.

Results: High-frequency K-ras mutation (2+ or 3+) was detected in the pancreas of all the 8 patients and in the pancreatic juice of the other 2 patients. The mutation in codon 12 of the ras gene was GAT in all the 10 patients. High-frequency K-ras mutation was detected in the common bile duct of 5 patients with AIP and in the gallbladder epithelium of 4 patients with AIP. The K-ras mutation was detected in the fibroinflammatory pancreas, the bile duct, and the gallbladder, with abundant infiltrating IgG4-positive plasma and Foxp3-positive cells of patients with AIP with elevated serum IgG4 levels.

Conclusions: Significant K-ras mutation occurs most frequently in the pancreatobiliary regions of patients with AIP. Autoimmune pancreatitis may be a risk factor of pancreatobiliary cancer.

MeSH terms

  • Aged
  • Autoimmune Diseases / genetics
  • Autoimmune Diseases / metabolism
  • Autoimmune Diseases / pathology*
  • Bile Ducts / metabolism
  • Chronic Disease
  • Digestive System / metabolism*
  • Female
  • Gallbladder / metabolism
  • Gene Frequency
  • Humans
  • Immunoglobulin G / blood
  • Immunoglobulin G / metabolism
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Mutation*
  • Pancreas / metabolism
  • Pancreatic Juice / metabolism
  • Pancreatitis / genetics
  • Pancreatitis / metabolism
  • Pancreatitis / pathology*
  • Pancreatitis, Alcoholic / genetics
  • Pancreatitis, Alcoholic / metabolism
  • Pancreatitis, Alcoholic / pathology
  • Plasma Cells / metabolism
  • Plasma Cells / pathology
  • ras Proteins / genetics*
  • ras Proteins / metabolism

Substances

  • Immunoglobulin G
  • ras Proteins