Gene mutations of K-ras in gallbladder mucosae and gallbladder carcinoma with an anomalous junction of the pancreaticobiliary duct.
OBJECTIVE
In this study, we examined the mutational spectrum of K-ras in cases of gallbladder and gallbladder carcinoma with an anomalous junction of the pancreaticobiliary duct (AJPBD).


METHODS
We examined 35 gallbladders with AJPBD (20 with hyperplasia, 15 with carcinoma) and 38 gallbladders without AJPBD (four normal gallbladders, four with hyperplasia, six with adenoma, 24 with carcinoma). Polymerase chain reaction single-strand conformation polymorphism (PCR-SSCP) and direct sequencing were performed to detect mutations in codon 12 or 13 of K-ras.


RESULTS
In the cases with AJPBD, the prevalences of K-ras mutation were 15% (3/20) in hyperplasia, 60% (6/10) in stage I carcinoma, and 100% (5/5) in stage II-IV carcinoma. In the cases without AJPBD, the prevalences of K-ras mutation were 0% (0/4) in normal gallbladder, 0% (0/4) in hyperplasia, 17% (1/6) in adenoma, 7% (1/16) in stage I carcinoma, and 38% (3/8) in stage II-IV carcinoma. Prevalences of K-ras mutation in hyperplasia and carcinoma with AJPBD were greater than those without AJPBD (p < 0.05). The point mutation of GGT to GAT in codon 12 was frequently observed in the cases with AJPBD.


CONCLUSIONS
These results suggest that the specific K-ras mutation in codon 12 (GGT to GAT) may contribute to the early stage of carcinogenesis in the gallbladder with AJPBD.
Hanada
K
K
Department of Internal Medicine, Onomichi General Hospital, Hiroshima University School of Medicine, Japan.
Tsuchida
A
A
Iwao
T
T
Eguchi
N
N
Sasaki
T
T
Morinaka
K
K
Matsubara
K
K
Kawasaki
Y
Y
Yamamoto
S
S
Kajiyama
G
G
D000236:Adenoma / Q000235:genetics; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001483:Base Sequence / Q000235:genetics; D001652:Bile Ducts / Q000002:abnormalities*; D002277:Carcinoma / Q000235:genetics; D005260:Female; D005704:Gallbladder / Q000473:pathology / Q000503:physiopathology*; D005706:Gallbladder Neoplasms / Q000235:genetics*; D005787:Gene Frequency; D011905:Genes, ras / Q000235:genetics*; D006801:Humans; D006965:Hyperplasia; D008297:Male; D008875:Middle Aged; D009092:Mucous Membrane / Q000473:pathology / Q000503:physiopathology; D010183:Pancreatic Ducts / Q000002:abnormalities*; D017354:Point Mutation / Q000235:genetics*; D012016:Reference Values