Clinicopathologic significance of the K‐ras gene codon 12 point mutation in stomach cancer. An analysis of 140 cases

Abstract

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. Cancer 1995;75:2794–2801. Copyright © 1995 American Cancer Society