Expression of epidermal growth factor receptor in gastric carcinomas.
OBJECTIVE
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.
Takehana
Takuo
T
Department of Pathology, Yamanashi Medical University, Japan.
Kunitomo
Kazuyoshi
K
Suzuki
Shioto
S
Kono
Koji
K
Fujii
Hideki
H
Matsumoto
Yoshiro
Y
Ooi
Akishi
A
D000230:Adenocarcinoma / Q000145:classification / Q000453:epidemiology / Q000378:metabolism*; D002288:Adenocarcinoma, Mucinous / Q000145:classification / Q000453:epidemiology / Q000378:metabolism*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis; D002291:Carcinoma, Papillary / Q000145:classification / Q000453:epidemiology / Q000378:metabolism*; D018279:Carcinoma, Signet Ring Cell / Q000145:classification / Q000453:epidemiology / Q000378:metabolism*; D004801:Eosine Yellowish-(YS); D066246:ErbB Receptors / Q000096:biosynthesis*; D005260:Female; D005456:Fluorescent Dyes; D005784:Gene Amplification; D006416:Hematoxylin; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D007564:Japan; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D015588:Observer Variation; D013223:Statistics as Topic; D013274:Stomach Neoplasms / Q000145:classification / Q000453:epidemiology / Q000378:metabolism*
D014408:Biomarkers, Tumor; D005456:Fluorescent Dyes; D066246:ErbB Receptors; D004801:Eosine Yellowish-(YS); D006416:Hematoxylin