Ki-ras codon 12 point mutation and p53 mutation in pancreatic diseases

BACKGROUND/AIMS: The Ki-ras gene located at 12p, encodes the GTP binding pr otein involving the signal transduction system and concerns cell proliferat ion and differentiation. METHODOLOGY: Pancreatic tissues were obtained from 37 patients with various pancreatic diseases. Ki-ras codon 12 point mutation and p53 (exon 5-8) mut ation were examined in 3 patients with chronic pancreatitis, 9 mucinous ade noma of the pancreas (2 with mucinous cystadenoma and 7 with intraductal pa pillary-mucinous adenoma), 22 pancreatic ductal carcinoma, and 3 serous cys tadenoma. RESULTS: On usual pancreatic exocrine ductal lesions, Ki-ras point mutation was evident in 0% (0/3) of chronic pancreatitis, in 56% (5/9) of mucinous adenoma, and in 57% (12/21) of ductal carcinoma, the mutation being located in the second letter in 18 and in the Ist letter in 2. One Ki-ras codon 12 positive pancreatic cancer showed Ki-ras codon 12 point mutation in the su rrounding pancreas (2nd letter mutation in both areas), p53 mutation was pr esent in 0% (0/1) of chronic pancreatitis, in 0% (0/8) of mucinous adenoma, while it was evident in 29% (6/21) of pancreatic ductal carcinoma, the mut ation being situated in exon 5 in 3, in exon 6 in 1, and in exon 7 in 2. In 3 patients with serous cystadenoma, there was no mutation in Ki-ras codon 12 or p53 (exon 5-8). CONCLUSIONS: These findings suggest that Ki-ras point mutation is involved in the early events of pancreatic ductal carcinoma, while p53 mutation is i ntricated in the late phase of pancreatic ductal carcinogenesis and the his togenesis of serous cystadenoma is different from that of pancreatic exocri ne ductal lesions including mucinous adenoma and ductal carcinoma.