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

Abstract

BACKGROUND Recent reports have described overexpression of p185c‐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. METHODS 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 p185c‐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 amplification by FISH, whereas p185c‐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 reflect intrinsic variations in antibody clones, or might suggest that, in some cases, the occurrence of protein overexpression is independent of gene amplification. Cancer 2001;92:677–83. © 2001 American Cancer Society.

Evaluation of the predictive value of Her-2/neu gene expression on osteosarcoma therapy in laser-microdissected paraffin-embedded tissue

“…Her-2/neu gene expression in osteosarcoma J Fellenberg et al protein and mRNA expression in osteosarcoma tissue. 20,21 The reasons for these conflicting data have been extensively discussed in the literature and attributed mainly to methological and technical issues. In most studies, immunohistochemistry has been used for the detection of Her-2/neu expression on sections derived from paraffin-embedded tissue.…”

“…In these studies, observation of cytoplasmic positivity was independent of histologic subtype and grade and not associated with response to preoperative chemotherapy or disease progression. 21,22 On the other hand, a correlation of cytoplasmic Her-2/neu positivity with a shorter overall metastasis-free survival has recently been reported. 23 These discrepancies have extensively been discussed in the literature and attributed mainly to technical issues including the type of tissue, fixation method, storage conditions, sensitivity and reliability of the antibodies used, the scoring system and the interpretation of the results.…”

Clinicopathologic Analysis of HER-2/neu Immunoexpression among Various Histologic Subtypes and Grades of Osteosarcoma

“…Recently, among 22 pretreatment osteosarcoma samples, Zhou and colleagues (18) reported a correlation between "cytoplasmic staining" of HER-2/neu and increased risk of pulmonary metastasis. Maitra and others (19) evaluated 18 high grade osteosarcomas using both immunohistochemistry and FISH analysis. Immunohistochemical overexpression of HER-2/neu was not observed.…”

“…Immunohistochemical overexpression of HER-2/neu was not observed. Furthermore, by FISH analysis, no evidence of amplification of the HER-2/neu oncogene was seen (19). In our series, we evaluated prechemotherapy samples (if applicable) from 41 osteosarcoma cases, 25 of which represented the conventional high-grade form.…”

Specific Tyrosine Kinase Inhibitors Regulate Human Osteosarcoma Cells In vitro

“…Several reports established an association between HER-2 expression and decreased overall patient survival [20,45,49], whereas others failed to confirm any association [1,43]. However, this does not undermine the potential benefit that inhibitors of tyrosine kinases may play in future treatment of patients with osteosarcoma.…”