title: A proposal for diagnostically meaningful criteria to classify increased epidermal growth factor receptor and c-erbB-2 gene copy numbers in gastric carcinoma, based on correlation of fluorescence in situ hybridization and immunohistochemical measurements.
abstract: Amplification of the epidermal growth factor receptor (EGFR) and/or c-erbB-2 oncogenes and overexpression of their proteins are detected in 30% of gastric carcinomas, but there are few reports regarding the correlation between gene amplification and protein overexpression. We examined the correlation between amplification of the EGFR and c-erbB-2 genes, detected using fluorescence in situ hybridization, and overexpression of their proteins, detected using immunohistochemistry, in formalin-fixed tissue sections of 54 surgically resected gastric carcinomas. A mean EGFR copy number per nucleus of four or more and an EGFR/chromosome 7 centromere (CEP7) ratio of 1.7 or more were each detected in 4 specimens (7%). The sensitivity and specificity of both criteria for EGFR protein overexpression were 75% and 92%, respectively. A mean c-erbB-2 copy number per nucleus of 7.0 or more and a c-erbB-2/chromosome 17 centromere (CEP17) ratio of 2.0 or more were detected in six (11%) and eight (15%) specimens, respectively. The sensitivity and specificity of the former criterion to c-erbB-2 overexpression were 83% and 98%, respectively, while those of the latter were 63% and 98%. A mean EGFR gene copy number of 4.0 or more and/or an EGFR/CEP7 ratio of 1.7 and a mean c-erbB-2 gene copy number of 7.0 or more and/or a c-erbB-2/CEP17 ratio of 2.0 or more would be useful in defining increased EGFR and c-erbB-2 gene copy numbers, respectively, in gastric carcinomas.
authors.affiliation: Department of Pathology II, National Defense Medical College, 3-2 Namiki, Tokorozawa, 359-8513 Saitama, Japan.
authors.forename: Mikihiko
authors.initials: M
authors.lastname: Kimura
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Tsuda
authors.forename: Daisaku
authors.initials: D
authors.lastname: Morita
authors.forename: Takashi
authors.initials: T
authors.lastname: Ichikura
authors.forename: Sho
authors.initials: S
authors.lastname: Ogata
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Aida
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Yoshizumi
authors.forename: Tadaaki
authors.initials: T
authors.lastname: Maehara
authors.forename: Hidetaka
authors.initials: H
authors.lastname: Mochizuki
authors.forename: Osamu
authors.initials: O
authors.lastname: Matsubara
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics*; D066246:ErbB Receptors / Q000145:classification* / Q000235:genetics*; D018628:Gene Dosage; D018734:Genes, erbB-2 / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D012680:Sensitivity and Specificity; D013274:Stomach Neoplasms / Q000235:genetics*
chemical_list: D066246:ErbB Receptors