Amplification of the HER-2/neu oncogene is uncommon in pediatric osteosarcomas

Recent reports have described overexpression of p185(c-erbB2), the product of the HER-2/neu oncogene, in more than 40% of archival osteosarcomas that were examined by immunohistochemistry (IHC). However, IHC can be influenced by the method of fixation, extent of antigen retrieval, specificity and sensitivity of the antibody clone, and the use of an arbitrary semiquantitative scoring system. In contrast, fluorescence in situ hybridization (FISH) assays that assess HER-2/neu gene copy numbers in individual cells are more consistent, more reproducible, and less subjective than IHC.

The authors examined pretreatment nondecalcified archival tissue from 21 high-grade pediatric osteosarcomas for amplification of the HER-2/neu oncogene using an Food and Drug Administration (FDA)-approved FISH assay (PathVysion, Vysis Inc., Downers Grove, IL). Additionally, IHC for p185(c-erbB2) was performed in all cases using the Dako polyclonal antibody clone A0485 (Dako Co., Carpinteria, CA).

None of the 21 osteosarcomas had evidence of HER-2/neu gene amplification by FISH, whereas p185(c-erbB2) IHC was negative in all cases.

HER-2/neu gene amplification appeared to be an uncommon event in pediatric osteosarcomas. The reason(s) for discordance between previous IHC data and the current FISH and IHC results was unknown, but might reflect intrinsic variations in antibody clones, or might suggest that, in some cases, the occurrence of protein overexpression is independent of gene amplification.