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

BACKGROUND. Recent reports have described overexpression of p185(c-erbB2), the product of the HER-2/neu oncogene, in more than 40% of archival osteosa rcomas that were examined by immunohistochemistry (IHC). However, IHC can b e influenced by the method of fixation, extent of antigen retrieval, specif icity and sensitivity of the antibody clone, and the use of an arbitrary se rniquantitative scoring system. In contrast, fluorescence in situ hybridiza tion (FISH) assays that assess HER-2/neu gene copy numbers in individual ce lls are more consistent, more reproducible, and less subjective than IHC. METHODS. The authors examined pretreatment nondecalcified archival tissue f rom 21 high-grade pediatric osteosarcomas for amplification of the HER-2/ne u oncogene using an Food and Drug Administration (FDA)-approved FISH assay (Path-Vysion, 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). RESULTS. None of the 21 osteosarcomas had evidence of HER-2/neu gene amplif ication by FISH, whereas p185(c-erbB2) IHC was negative in all cases. CONCLUSIONS. 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 reflec t intrinsic variations in antibody clones, or might suggest that, in some c ases, the occurrence of protein overexpression is independent of gene ampli fication. Cancer 2001;92: 677-83. (C) 2001 American Cancer Society.