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.
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.
Kimura
Mikihiko
M
Department of Pathology II, National Defense Medical College, 3-2 Namiki, Tokorozawa, 359-8513 Saitama, Japan.
Tsuda
Hitoshi
H
Morita
Daisaku
D
Ichikura
Takashi
T
Ogata
Sho
S
Aida
Shinsuke
S
Yoshizumi
Yutaka
Y
Maehara
Tadaaki
T
Mochizuki
Hidetaka
H
Matsubara
Osamu
O
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*
D066246:ErbB Receptors