Detection of c-erbB-2 (HER-2/neu) amplification in breast carcinoma by fluorescence in situ hybridization on tissue sections and imprinted cells.
Abnormalities in c-erbB-2 have attracted a great deal of attention. Treatment using an antibody against the c-erbB-2 gene product is effective against breast cancers with amplification and/or overexpression of c-erbB-2. There is an urgent need to establish methodology for selecting patients who would benefit from this therapy. A total of 235 breast carcinomas were examined for c-erbB-2 protein overexpression by immunohistochemistry. Tissue sections with discernible immunostaining from 52 tumors, 70 negative tumors and smear imprints from 35 patients were examined by dual-color fluorescence in situ hybridization (FISH) using probes specific for c-erbB-2 and the centromeric region of chromosome 17. The concordance between gene amplification and protein overexpression was 95.7%. When the findings of the two FISH preparation techniques were compared, no discrepancies were found in 24 of the tumors. However, differences were seen in eight cases. In six of these cases the differences did not affect the presence or absence of amplification, but in the other two cases, considered to show low-level amplification on paraffin sections, polysomy 17 was detected instead. It was concluded that FISH is an excellent tool to detect gene amplification in particular, and FISH on touch imprints is a useful adjunct to differentiate between low-level amplification and polysomy 17.
Kunitomo
KazuyoshI
K
Department of Pathology, Yamanashi Medical University, Yamanashi, Japan, Department of Surgery, Yamanashi Medical University, Yamanashi, Japan.
Takehana
Takuo
T
Inoue
Shingo
S
Fujii
Hideki
H
Suzuki
Shioto
S
Matsumoto
Yoshiro
Y
Ooi
Akishi
A
D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics; D003937:Diagnosis, Differential; D005784:Gene Amplification; D018734:Genes, erbB-2 / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D016612:Paraffin Embedding; D013048:Specimen Handling