Amplification of the c-erbB-2 (HER-2/neu) gene in gastric cancer cells. Detection by fluorescence in situ hybridization.
Amplification of the c-erbB-2 gene was examined in 120 gastric adenocarcinomas by dual-color fluorescence in situ hybridization (FISH) using probes for centromere 17 and the 17q11.2-12. The results were compared with Southern blot analysis and immunohistochemistry of c-erbB-2 overexpression. FISH was successful in 105 tumors, and the amplification was found in 19 tumors. FISH on 17 tumors revealed high-level amplification; in 15, the predominant cancer populations had amplified c-erbB-2 gene with the signals forming one or two clusters, indicating that the amplified gene was present in homogeneously staining regions. In two tumors, most cancer cells had multiple scattered c-erbB-2 signals, indicating that the amplicon was within double-minute chromosomes. The other two tumors had a few additional copies of the c-erbB-2 gene. Seventeen tumors had increased numbers of the gene probably due to polysomy 17, and sixty-nine tumors had no aberrations of chromosome 17. Immunohistochemically, distinct membrane staining was found only in the 17 tumors with the high-level amplification. It is concluded that, in gastric adenocarcinomas, high-level amplification produces the c-erbB-2 gene principally in homogeneously staining region form and occasionally in double-minute form and is thought to control the over-expression of the protein in the cytoplasmic membrane.
Ishikawa
T
T
Department of Pathology, Faculty of Medicine, Kanazawa University, Ishikawa, Japan.
Kobayashi
M
M
Mai
M
M
Suzuki
T
T
Ooi
A
A
D000230:Adenocarcinoma / Q000235:genetics*; D015139:Blotting, Southern; D002886:Chromosomes, Human, Pair 17; D005784:Gene Amplification; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism; D013274:Stomach Neoplasms / Q000235:genetics* / Q000378:metabolism; D014407:Tumor Cells, Cultured
D018719:Erb-b2 Receptor Tyrosine Kinases