This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Thomas, D. G. Articles by Baker, L. Search for Related Content PubMed PubMed Citation Articles by Thomas, D. G. Articles by Baker, L.

Absence of HER2/neu Gene Expression in Osteosarcoma and Skeletal Ewing’s Sarcoma¹

Departments of Pathology [D. G. T., T. J. G., D. S.], Orthopedic Surgery [J. S. B.], and Internal Medicine [L. B.], University of Michigan Health System, Ann Arbor, Michigan 48109-0602

Purpose: 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.

Experimental Design and 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.

This article has been cited by other articles:

				S Apostolaki, M Perraki, A Pallis, V Bozionelou, S Agelaki, P Kanellou, A Kotsakis, E Politaki, K Kalbakis, A Kalykaki, et al. Circulating HER2 mRNA-positive cells in the peripheral blood of patients with stage I and II breast cancer after the administration of adjuvant chemotherapy: evaluation of their clinical relevance Ann. Onc., May 1, 2007; 18(5): 851 - 858. [Abstract] [Full Text] [PDF]

				R. J. Gilbertson ERBB2 in Pediatric Cancer: Innocent Until Proven Guilty Oncologist, August 1, 2005; 10(7): 508 - 517. [Abstract] [Full Text] [PDF]

				M. R. Verneris, A. Arshi, M. Edinger, M. Kornacker, Y. Natkunam, M. Karami, Y.-a. Cao, N. Marina, C. H. Contag, and R. S. Negrin Low Levels of Her2/neu Expressed by Ewing's Family Tumor Cell Lines Can Redirect Cytokine-Induced Killer Cells Clin. Cancer Res., June 15, 2005; 11(12): 4561 - 4570. [Abstract] [Full Text] [PDF]

				H. Guan, S.-F. Jia, Z. Zhou, J. Stewart, and E. S. Kleinerman Herceptin Down-Regulates HER-2/neu and Vascular Endothelial Growth Factor Expression and Enhances Taxol-Induced Cytotoxicity of Human Ewing's Sarcoma Cells In vitro and In vivo Clin. Cancer Res., March 1, 2005; 11(5): 2008 - 2017. [Abstract] [Full Text] [PDF]

				V. Bozionellou, D. Mavroudis, M. Perraki, S. Papadopoulos, S. Apostolaki, E. Stathopoulos, A. Stathopoulou, E. Lianidou, and V. Georgoulias Trastuzumab Administration Can Effectively Target Chemotherapy-Resistant Cytokeratin-19 Messenger RNA-Positive Tumor Cells in the Peripheral Blood and Bone Marrow of Patients With Breast Cancer Clin. Cancer Res., December 15, 2004; 10(24): 8185 - 8194. [Abstract] [Full Text] [PDF]

				D. P. M. Hughes, D. G. Thomas, T. J. Giordano, L. H. Baker, and K. T. McDonagh Cell Surface Expression of Epidermal Growth Factor Receptor and Her-2 with Nuclear Expression of Her-4 in Primary Osteosarcoma Cancer Res., March 15, 2004; 64(6): 2047 - 2053. [Abstract] [Full Text] [PDF]

				B. Fuchs, C. Y. Inwards, and R. Janknecht Vascular Endothelial Growth Factor Expression is Up-Regulated by EWS-ETS Oncoproteins and Sp1 and May Represent an Independent Predictor of Survival in Ewing's Sarcoma Clin. Cancer Res., February 15, 2004; 10(4): 1344 - 1353. [Abstract] [Full Text] [PDF]

				H. R. Dhaini, D. G. Thomas, T. J. Giordano, T. D. Johnson, J. S. Biermann, K. Leu, P. F. Hollenberg, and L. H. Baker Cytochrome P450 CYP3A4/5 Expression as a Biomarker of Outcome in Osteosarcoma J. Clin. Oncol., July 1, 2003; 21(13): 2481 - 2485. [Abstract] [Full Text] [PDF]