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American Journal of Pathology, Vol 151, 761-768, Copyright © 1997 by American Society for Investigative Pathology

REGULAR ARTICLES

Amplification of the c-erbB-2 (HER-2/neu) gene in gastric cancer cells. Detection by fluorescence in situ hybridization

T Ishikawa, M Kobayashi, M Mai, T Suzuki and A Ooi
Department of Pathology, Faculty of Medicine, Kanazawa University, Ishikawa, Japan.

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.

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