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Gene amplification in gastric and esophageal adenocarcinomas
J Houldsworth1, C Cordon-Cardo, M Ladanyi
1Laboratory of Cancer Genetics, Memorial Sloan-Kettering Cancer Center, New York, New York 10021.
Abstract:
In a United States series of 28 gastric/esophageal adenocarcinomas of poorly to moderately differentiated histopathology, we detected gene amplification in 21% of the tumors. Using the modified DNA in-gel renaturation assay to detect down to 7-8 copies of amplified DNA sequences, we identified 3 gastric tumors with amplified DNA sequences and confirmed by Southern hybridization analysis that HER-2/neu was amplified greater than 5-fold in these specimens. Immunohistochemical staining of tumor tissue sections with p185 HER-2/neu antibodies demonstrated that only the 3 gastric adenocarcinomas with corresponding HER-2/neu gene amplification displayed membrane immunoreactivity. Amplification of c-met was identified in 2 tumors, and this was the first study to assay for multiple copies of this protooncogene in fresh gastric tumor tissues. Amplification of c-erbB was observed in one tumor, and no evidence for amplification of int-2 was obtained in this series of adenocarcinomas.
Insights
Gene amplification, including HER-2/neu, was found in 21% of gastric/esophageal adenocarcinomas. HER-2/neu gene amplification correlated with membrane protein expression in gastric tumors, suggesting its potential role.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Gastric and esophageal adenocarcinomas are significant health concerns.
- Gene amplification is a known mechanism in cancer development.
- Specific protooncogenes like HER-2/neu, c-met, and c-erbB are implicated in various cancers.
Purpose of the Study:
- To investigate the frequency of gene amplification in gastric/esophageal adenocarcinomas.
- To determine if HER-2/neu gene amplification correlates with protein expression.
- To assess the amplification status of c-met and c-erbB protooncogenes in these tumors.
Main Methods:
- Analysis of 28 gastric/esophageal adenocarcinomas using modified DNA in-gel renaturation assay.
- Southern hybridization for confirmation of gene amplification.
- Immunohistochemical staining with p185 HER-2/neu antibodies.
Main Results:
- Gene amplification was detected in 21% of the tumors studied.
- HER-2/neu gene amplification (greater than 5-fold) was identified in 3 gastric tumors.
- HER-2/neu gene amplification correlated with membrane immunoreactivity of the p185 HER-2/neu protein.
- Amplification of c-met was found in 2 tumors, and c-erbB in one tumor.
- No amplification of int-2 was observed.
Conclusions:
- Gene amplification, particularly of HER-2/neu, occurs in a subset of gastric/esophageal adenocarcinomas.
- HER-2/neu gene amplification is associated with its protein expression, indicating potential therapeutic relevance.
- This study provides initial evidence for c-met and c-erbB amplification in gastric tumors.