K-ras and p53 mutations in stage I gallbladder carcinoma with an anomalous junction of the pancreaticobiliary duct.
BACKGROUND
An anomalous junction of the pancreaticobiliary duct (AJPBD) was thought to be an important risk factor for gallbladder carcinoma in Japan. In this report, we compared K-ras and p53 mutations in Stage I gallbladder carcinomas (GC) of patients with AJPBD with those in patients without AJPBD:


METHODS
We examined 6 GC of patients with AJPBD and 20 GC of patients without AJPBD: Immunohistochemistry was performed for p53 protein. K-ras and p53 mutations were examined using genomic DNA extracted from the cancer regions. The methods of polymerase chain reaction (PCR) single strand conformation polymorphism analysis were performed for mutations in exons 5-8 of p53. The methods of PCR restriction fragment length polymorphism were performed for mutation in codon 12 of K-ras.


RESULTS
p53 positivity was 67% in GC of patients with AJPBD and 65% in GC of patients without AJPBD: p53 mutations were found in exons 7 and 8 in GC of patients with AJPBD and in exons 5, 6, and 7 in GC of patients without AJPBD: The incidence of K-ras mutation in GC of patients with AJPBD (50%) was greater than that in patients without AJPBD (6%) (P < 0.05).


CONCLUSIONS
These results suggest that K-ras mutation may be important in the early stage of carcinogenesis of the gallbladder mucosa with AJPBD, and that p53 mutations may also contribute to the early stage of carcinogenesis of the gallbladder mucosa, regardless of AJPBD:
Hanada
K
K
First Department of Internal Medicine, Hiroshima University School of Medicine, Japan.
Itoh
M
M
Fujii
K
K
Tsuchida
A
A
Ooishi
H
H
Kajiyama
G
G
D000230:Adenocarcinoma / Q000150:complications / Q000235:genetics*; D000231:Adenocarcinoma, Papillary / Q000150:complications / Q000235:genetics*; D000328:Adult; D000368:Aged; D001483:Base Sequence; D003135:Common Bile Duct / Q000002:abnormalities*; D005260:Female; D005706:Gallbladder Neoplasms / Q000150:complications / Q000235:genetics*; D016158:Genes, p53; D011905:Genes, ras; D006801:Humans; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D009367:Neoplasm Staging; D010183:Pancreatic Ducts / Q000002:abnormalities*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012307:Risk Factors; D016159:Tumor Suppressor Protein p53 / Q000032:analysis
D016159:Tumor Suppressor Protein p53