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


RESULTS
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.


CONCLUSIONS
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.
Thomas
Dafydd G
DG
Department of Pathology, University of Michigan Health System, Ann Arbor, Michigan 48109-0602, USA. Thomasda@med.umich.edu
Giordano
Thomas J
TJ
Sanders
Donita
D
Biermann
J Sybil
JS
Baker
Laurence
L
D000293:Adolescent; D000328:Adult; D000368:Aged; D001859:Bone Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002454:Cell Differentiation; D002648:Child; D017931:DNA Primers / Q000737:chemistry; D005260:Female; D015870:Gene Expression; D006801:Humans; D007124:Immunoenzyme Techniques; D008175:Lung Neoplasms / Q000556:secondary; D008297:Male; D008875:Middle Aged; D012516:Osteosarcoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D012334:RNA, Neoplasm / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012512:Sarcoma, Ewing / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
D017931:DNA Primers; D012334:RNA, Neoplasm; D018719:Erb-b2 Receptor Tyrosine Kinases