To evaluate whether it is useful for diagnosis to detect K-ras and p53 muta
tions in biopsy specimens and bile of biliary tract lesions, 12 cholangioca
rcinomas (CC), eight cases of cholangitis, seven gallbladder carcinomas (GB
C), seven gallbladder cholesterol polyps, four cases of adenomyomatosis of
the gallbladder and five cases of cholecystitis were examined. K-ras and p5
3 mutations in bile were detected by a two-step polymerase chain reaction (
PCR) and nested PCR-single-strand conformation polymorphism (SSCP) analysis
, In addition, p53 protein expression in biopsy specimens from CC were exam
ined by immunostaining, K-ras mutations at codon 12 were detected in 50% of
CC and 57.1% of GBC in both biopsy specimens and bile. The incidence of p5
3 mutations was 33.3% in CC and 42.9% in GBC, p53 protein overexpression wa
s observed in 60% CC biopsy specimens. In contrast, K-ras and p53 abnormali
ties were not detected in any non-neoplastic biliary tract lesion. K-ras an
d p53 mutations in biliary tract cancers showed the same mutation patterns
in spite of differences in the collection methods used between bile and bio
psy specimens or surgically resected tissue, Genetic analysis of K-ras and
p53 mutations in biopsy specimens and bile may be useful for the diagnosis
of biliary tract cancers, although it may be effectively limited to patient
s with advanced disease.