Frequent and significant K-ras mutation in the pancreas, the bile duct, and the gallbladder in autoimmune pancreatitis.
OBJECTIVE
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.
Kamisawa
Terumi
T
Department of Internal Medicine, Tokyo Metropolitan Komagome Hospital, Tokyo, Japan. kamisawa@cick.jp
Tsuruta
Kouji
K
Okamoto
Atsutake
A
Horiguchi
Shin-ichirou
S
Hayashi
Yukiko
Y
Yun
Xiaoqing
X
Yamaguchi
Toshikazu
T
Sasaki
Tsuneo
T
D000368:Aged; D001327:Autoimmune Diseases / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D001652:Bile Ducts / Q000378:metabolism; D002908:Chronic Disease; D004064:Digestive System / Q000378:metabolism*; D005260:Female; D005704:Gallbladder / Q000378:metabolism; D005787:Gene Frequency; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000378:metabolism; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010179:Pancreas / Q000378:metabolism; D010189:Pancreatic Juice / Q000378:metabolism; D010195:Pancreatitis / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D019512:Pancreatitis, Alcoholic / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D010950:Plasma Cells / Q000378:metabolism / Q000473:pathology; D018631:ras Proteins / Q000235:genetics* / Q000378:metabolism
D007074:Immunoglobulin G; D018631:ras Proteins