Clinicopathologic significance of the K-ras gene codon 12 point mutation in stomach cancer. An analysis of 140 cases.
BACKGROUND
The frequency and clinicopathologic significance of the K-ras gene point mutation in stomach cancer remain to be defined.


METHODS
The authors investigated the frequency of K-ras codon 12 point mutations in stomach cancer using a sensitive polymerase chain reaction (PCR)-based method in 140 samples and correlated the findings with various clinicopathologic characteristics of the patients.


RESULTS
The overall frequency of K-ras codon 12 point mutations in stomach cancer was 7.9% (11/140). DNA sequencing of nine cases with K-ras codon 12 point mutations identified seven cases with a single-base substitution of GGT to AGT (glycine to serine) and two with single-base substitution of GGT to AGT (aspartic acid). Tumors located in the upper third of the stomach had a significantly higher frequency of K-ras codon 12 mutations (3/8, 37.5%) compared with tumors located in the middle (4/29, 13.8%) or lower (3/99, 3.0%) thirds of the stomach (P = 0.001). No significant difference was observed in the frequency of K-ras codon 12 mutations in terms of other various clinicopathologic characteristics including tumor DNA ploidy and S-phase fraction. After a median follow-up of 26 months, disease free and overall survival were not significantly different between patients with stomach cancer with or without K-ras codon 12 mutation. Among eight patients with stomach cancer located in the upper part of the stomach, none of the three patients with K-ras gene-mutated tumors died versus four of five with tumors without K-ras gene mutations (P = 0.064).


CONCLUSIONS
K-ras codon 12 point mutations are uncommon in stomach cancer (7.9%). There was significant correlation between K-ras mutations and vertical tumor location in the stomach, suggesting that different mechanisms may play a role in the pathogenesis of stomach cancer according to the location of tumors in the stomach.
Lee
K H
KH
Department of Medicine, Asan Medical Center, College of Medicine, University of Ulsan, Seoul, Korea.
Lee
J S
JS
Suh
C
C
Kim
S W
SW
Kim
S B
SB
Lee
J H
JH
Lee
M S
MS
Park
M Y
MY
Sun
H S
HS
Kim
S H
SH
D000328:Adult; D000368:Aged; D001483:Base Sequence; D003062:Codon; D004273:DNA, Neoplasm / Q000032:analysis; D005260:Female; D005434:Flow Cytometry; D011905:Genes, ras; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D017354:Point Mutation; D012150:Polymorphism, Restriction Fragment Length; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology
D003062:Codon; D004273:DNA, Neoplasm