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The Korean Journal of Pathology 2002;36(2): 77-83.
Ras Gene Mutations and Expression of ERK1 and ERK2 Proteins in Stomach Cancer.
Jinyoung Yoo, Seok Jin Kang, Byung Kee Kim, Chang Suk Kang
Department of Pathology, College of Medicine, The Catholic University of Korea, Seoul, Korea. sjkang@vincent.cuk.ac.kr
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.
Key Words: Stomach Neoplasms-Genes; ras-MAP Kinase Signaling System