Original article
Expression of epidermal growth factor receptor in gastric carcinomas

https://doi.org/10.1016/S1542-3565(03)00219-2Get rights and content

Abstract

Background & Aims: Epidermal growth factor receptor belongs to the family of type I receptor tyrosine kinases. Overexpression of epidermal growth factor receptor has been observed in a variety of cancers with or without amplification of the gene. Novel chemotherapies targeting receptor tyrosine kinases might be effective for the treatment of cancers in which overexpression of this protein is a feature. The aim of this study was to assess the potential efficacy of epidermal growth factor receptor-targeted therapy in gastric cancer. This was achieved by determining the frequency of increased epidermal growth factor receptor expression in gastric cancers and investigating the relationship between protein overexpression and gene amplification. Methods: Immunohistochemical evaluation of 413 gastric cancers was carried out by using a monoclonal antibody to the epidermal growth factor receptor. The intensity of reactivity was scored by using a 4-tier system (negative, 1+, 2+, and 3+). All positive staining (>1+) tumors overexpressing the protein were then analyzed for gene amplification by fluorescence in situ hybridization by using a gene-specific probe. Results: High levels of overexpression (2+ or 3+ staining) were found in 9 of 413 (2.2%) patients, whereas low levels of overexpression (1+) were found in 34 (8.2%) of the study cohort. Fluorescence in situ hybridization analysis showed that more than 10 copies of the gene were recognized in all 5 cancers with 3+ staining and in 2 of the 4 tumors with 2+ staining. Conclusions: Although a high level of overexpression of epidermal growth factor receptor is uncommon in gastric carcinomas, it almost exclusively occurs by gene amplification.

Section snippets

Patients and tissue samples

We examined 413 gastric carcinomas resected consecutively at the Department of Surgery, Yamanashi Medical University between 1994 and 2000. The patients included 290 men and 123 women with an average age of 63.2 years (range, 18–90 years). This laboratory study was approved by the Institutional Review Board of Yamanashi Medical University, and written, informed consent was obtained from all patients. By using the criteria of the World Health Organization Classification of Tumors,29 the 413

Results

Positive immunostaining of the EGFR protein (1+, 2+, or 3+) was found in 43 (10.4%) of the 413 gastric carcinomas analyzed. The distinction between 1+ and negative staining was equivocal in 12 cases with variance between the 3 pathologists. High-level overexpression (2+ or 3+) was found in 9 carcinomas (2.2%) and differed from 1+ staining in that it was distinct (Figure 1A) and was graded consistently by the pathologists. Comparison of extracellular domain- and intracellular domain-specific

Discussion

In this study, high-level overexpression of EGFR was found in a small minority (2.2%) of gastric cancers. Earlier studies have reported a higher prevalence of EGFR overexpression in gastric cancers detected by IHC ranging from 18%–81%,14, 15, 16, 17, 18, 19, 20, 21 although some of these findings remain controversial. In comparison with these other studies, we observed a considerably smaller rate of overall positivity (i.e., 10.4%) and high-level overexpression. This variation might be related

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