Absence of HER2/neu gene expression in osteosarcoma and skeletal Ewing's sarcoma.

Abstract

Osteosarcoma (OS) and skeletal Ewing's sarcoma (EWS), the most common pediatric primary bone tumors, are aggressive malignancies with a tendency for early pulmonary metastasis. Advances in therapy have increased the overall 5-year survival to approximately 70%; however, patients who relapse often fail to respond to salvage therapy. Thus, more effective adjuvant chemotherapy is needed for these patients. Several reports have claimed expression of the HER2/neu (c-erbB-2) gene in a high percentage of OSs and that its expression is a poor prognostic factor and have advocated monoclonal antibody therapy in those cases. To validate the expression of HER2/neu in these tumors, archival cases of OS (n = 66) and EWS (n = 11) from 44 patients were assessed for HER2/neu gene expression by immunohistochemistry (DAKO rabbit polyclonal antibody A0485). Thirty-four cases (44%) demonstrated granular cytoplasmic staining, but none showed the distinct membranous staining characteristic of expression exhibited by breast carcinomas. To validate these immunohistochemical results, reverse transcription-PCR using RNA derived from archival material (n = 48) and several different primer pairs also failed to demonstrate the presence of amplifiable HER2/neu mRNA, although a known HER2/neu-positive breast carcinoma showed amplifiable mRNA. Thus, in contrast to previous reports, our results demonstrate an absence of HER2/neu expression in OSs and EWSs. Our results show that HER2/neu is not expressed by these sarcomas, and we conclude that HER2/neu is therefore not an important prognostic factor and that anti-HER2/neu monoclonal antibody therapy is not appropriate for these patients.