Amplification of Epidermal Growth Factor Receptor Gene and Its Relationship to Survival in Human Gastric Cancer

Abstract

The correlation between the clinical features in 103 patients with primary gastric carcinoma and amplification of epidermal growth factor receptor (EGFR) gene was analyzed retrospectively. EGFR gene amplification was examined by slot-blot hybridization using DNA extracted from formalin-fixed, paraffin-embedded tissues. EGFR expression was also examined immunohistochemi-cally using the same tissues with a monoclonal antibody that is monospecific for EGFR. In 5 of 103 cases (4.9%), a 2- to 11-fold amplification of EGFR gene was detected. Four of these 5 cases were poorly differentiated adenocarcinomas. All of them had overexpressions of EGFR. The cumulative survival rate of patients with EGFR gene amplification was significantly lower than that of the patients without amplification (p < 0.05) and all of them died within 3 years. Except for tumor size (p < 0.03), there were no significant clinicopa-thologic differences between the two groups. On the other hand, 41 of 103 cases (39.8%) exhibited expression of EGFR. However, there was no significant correlation between EGFR expression and clinicopathologic factors or prognosis. These results indicate that EGFR gene amplification may occur in advanced stages during the progression and be an important indicator of poor short-term prognosis in gastric carcinoma.

Meta-analysis of Six Randomized Control Trials of Chemotherapy Plus Anti-HER Monoclonal Antibody for Advanced Gastric and Gastroesophageal Cancer

“…The EGFR pathway has been recognized as one of the key proliferative pathways which was deregulated during tumorigenesis. EGFR over-expressed in 30% and up to 90% of gastric and oesophageal cancers (Yonemura et al, 1989;Hirono et al, 1995). There are two classes of anti-EGFR agents: the monoclonal antibodies and small-molecule tyrosine kinase inhibitors (Huang et al, 2004;Tabernero, 2007).…”

Epidermal growth factor receptor expression correlates with poor survival in gastric adenocarcinoma from Mexican patients: a multivariate analysis using a standardized immunohistochemical detection system

“…For gastric cancer, co-expression of EGFR and its ligands EGF or TGF-a was found to be correlated with a decrease of survival or the relapse-free survival interval. 4,17,19 Amplification 7,8 or expression of EGFR 4 was correlated with advanced clinical stage and the presence of lymph node metastasis.…”

“…Amplification of the EGFR gene has been described as a rare event in gastric carcinomas. [6][7][8] Mutations in the EGFR gene have been detected in glioblastomas, breast, ovarian, prostate and lung carcinomas, 9 but so far not in gastric carcinoma. Dysregulation of the EGFR signal transduction pathway is a clinical target for anticancer therapy.…”

Autophosphorylation of the carboxyl‐terminal domain is not required for oncogenic transformation by lung‐cancer derived EGFR mutants

“…Aberrant activation of EGFR is among the most common oncogenic driving events in human cancer, which is mediated largely through different classes of genomic alterations within the EGFR gene 2. These genomic events include somatic EGFR mutations within regions of either the extracellular domain, in glioblastoma, or the kinase domain in lung adenocarcinoma,3, 4 as well as through gene amplification as observed in many other types of solid tumors 5, 6. In addition, several intragenic deletions within either the extracellular or C‐terminal domain of EGFR have also been reported to be oncogenic in a subset of glioblastoma and lung adenocarcinoma 7, 8, 9…”