CLINICOPATHOLOGICAL 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. Method s. The authors investigated the frequency of K-ras codon 12 point muta tions in stomach cancer using a sensitive polymerase chain reaction (P CR)-based method in 140 samples and correlated the findings with vario us clinicopathologic characteristics of the patients. Results. The ove rall 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 G GT 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 mutatio ns (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 signifi cant difference was observed in the frequency of K-ras codon 12 mutati ons in terms of other various clinicopathologic characteristics includ ing tumor DNA ploidy and S-phase fraction. After a median follow-up of 26 months, disease free and overall survival were not significantly d ifferent between patients with stomach cancer with or without K-ras co don 12 mutation. Among eight patients with stomach cancer located in t he upper part of the stomach, none of the three patients with K-ras ge ne-mutated tumors died versus four of five with tumors without K-ras g ene mutations (P = 0.064). Conclusions. K-ras codon 12 point mutations are uncommon in stomach cancer (7.9%). There was significant correlat ion between K-ras mutations and vertical tumor location in the stomach , suggesting that different mechanisms may play a role in the pathogen esis of stomach cancer according to the location of tumors in the stom ach.