Ras Gene Mutations and Expression of ERK1 and ERK2 Proteins in Stomach Cancer

ABSTRACT

BACKGROUND: We investigated stomach cancers for ras abnormalities and expression of ERK1 and ERK2 to determine their significance in the tumor development and/or progression and to evaluate their potential correlation with clinicopathologic parameters. METHODS: Seventy gastric adenocarcinomas were studied immunohistochemically in paraffin-embedded tissue sections for the expression of ERK1 and ERK2 proteins. All tumors were further analyzed with the use of a polymerase chain reaction technique and a direct sequence analysis procedure for the presence of the mutated ras gene. RESULTS: ERK1 and/or ERK2 was expressed in 65.7% (46/70) of the tumors; overexpression of ERK1 was observed in 38 (54.3%) tumors, whereas ERK2 was detected in 29 (41.4%). Nine (12.8%) samples demonstrated multations in the ras gene 4 in H-ras and 5 in K-ras. Seven of the 9 (77.8%) mutated tumors were of the intestinal type. No association was established between the ras abnormalities and the overexpression of ERK1 and/or ERK2. However, the correlation between ERK2 and progression (early vs. advanced) was statistically significant (p<0.05). CONCLUSIONS: These data indicate that ras abnormalities are uncommon events in gastric adenocarcinomas. The majority of ras mutations, however, occurred in intestinal-type tumors, supporting the notion of different molecular mechanisms involved between the intestinal-and diffuse-type lesions. Enhanced ERK2 activity may provide assistance in the determination of tumor penetration in these tumors.