K-ras oncogene mutation in cancer and precancerous lesions of the gallbladder.
OBJECTIVE
To determine whether K-ras mutation plays any role in the development and progression of gallbladder cancer, or has any clinical or pathological significance in gallbladder cancer patients, we investigated the presence and incidence of this mutation in the normal mucosa, and precancerous and cancerous lesions of the gallbladder.


METHODS
DNA was obtained from normal mucosa, dysplastic mucosa, primary cancer tissues, and metastatic lymph nodes that were identified and microdissected from the paraffin blocks of 20 gallbladder cancer cases. K-ras codon 12 mutations were investigated using a modified two-step polymerase chain reaction and the restriction fragment length polymorphism method, and by direct sequencing with an automated sequencer.


RESULTS
K-ras mutations were detected in the tissues of 10 out of the 20 patients. A mutation was present in the dysplastic epithelium associated with the primary carcinoma in 3 out of 12 specimens, in metastatic carcinoma in 1 out of 5 patients, and in primary carcinoma in 8 out of 20 patients. Mutation was found only once in the dysplastic, noncancerous epithelium, and only once in a metastatic tumor although not detectable in the primary cancer. Direct sequencing showed that the mutations were G to C substitutions (GGT-->CGT) at the first site of codon 12, except in two cases (GGT-->TGT). There were no correlations between K-ras mutations and clinicopathological factors.


CONCLUSIONS
K-ras mutations were detected in half of the gallbladder cancer cases. We suggest that K-ras mutation may play a role in the development of premalignant lesions or early carcinogenesis in some gallbladder cancers. We were unable to find any evidence that K-ras mutation plays any role in tumor progression or metastasis, or that it has any clinicopathological significance.
Kim
S W
SW
Department of Surgery, Seoul National University College of Medicine, Seoul, Korea.
Her
K H
KH
Jang
J Y
JY
Kim
W H
WH
Kim
Y T
YT
Park
Y H
YH
D000328:Adult; D000368:Aged; D005260:Female; D005706:Gallbladder Neoplasms / Q000235:genetics* / Q000473:pathology; D011905:Genes, ras / Q000235:genetics*; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009154:Mutation; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D011230:Precancerous Conditions / Q000235:genetics*