Association of K-ras mutations with liver metastases from colorectal carcinoma.
BACKGROUND
Colorectal carcinomas were studied regarding early proof of liver metastases through determination of K-ras mutations.


METHODS
Seventy-seven colorectal carcinomas were investigated for the presence of point mutations in codon 12 and 13 of the K-ras gene, using single-strand conformation polymorphism (SSCP) analysis and direct sequencing.


RESULTS
Twenty-six carcinomas were positive for K-ras mutations, of which 21 had codon 12 and 5 had codon 13 mutations. Twenty patients with K-ras-positive tumor (20 out of 26: 77%) developed liver metastases, of which 13 had simultaneous metastases and 7 had metachronous metastases. There was a significant association between K-ras mutations and liver metastases (p=0.03). A multivariate logistic regression model demonstrated that the involvement of lymph node (p<0.01) and K-ras mutations (p=0.02) were predictive factors for liver metastases from colorectal carcinoma. Sequencing in carcinomas without liver metastases showed the base change in the first position of codon 12, whereas with liver metastases it showed significantly frequent base change in the second position of codon 12 (p<0.01).


CONCLUSIONS
It is suggested that the presence of K-ras mutation, especially base change in the second position of codon 12, may predict liver metastases from colorectal carcinoma.
Second Department of Surgery, School of Medicine, Showa University, Tokyo, Japan. at1151@mx10.ttcn.ne.jp
Akira
A
Tsunoda
Takeru
T
Iijima
Yuko
Y
Tsunoda
Kentaroh
K
Nakao
Michiko
M
Miyaki
Mitsuo
M
Kusano
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology*; D005260:Female; D011905:Genes, ras / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000556:secondary*; D008297:Male; D008875:Middle Aged; D017354:Point Mutation; D011237:Predictive Value of Tests