Prognostic and therapeutic relevance of HER2 expression in osteosarcoma and Ewing's sarcoma

Eur J Cancer. 2005 Jun;41(9):1349-61. doi: 10.1016/j.ejca.2005.03.015.


Expression of HER2 was evaluated by immunohistochemical techniques in 84 osteosarcoma (OS) and 113 Ewing's sarcoma (ES) paraffin-embedded tumour biopsies. HER2 gene status was also assessed in a panel of cell lines as well as in vitro efficacy of trastuzumab (a humanised antibody directed against HER2) as single agent or in combination with the insulin-like growth factor I receptor (IGF-IR) IR3 antibody. Overexpression of HER2 was present in 32% of OS and 16% of ES and was significantly associated with the increased expression of P-glycoprotein, a surface molecule responsible for multidrug resistance. Event-free survival analyses revealed a prognostic value for HER2 and/or P-glycoprotein expression in OS, but not in ES. However, despite its prognostic relevance, no therapeutic effectiveness was observed pre-clinically for trastuzumab-driven therapy, in both OS or ES cell lines, unless the antibody was associated with anti-IGF-IR targeting strategies. Therefore, the therapeutic potential of trastuzumab in these neoplasms may be better exploited in combined treatments with anti-IGF-IR approaches.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism
  • Adolescent
  • Adult
  • Antibodies, Monoclonal / therapeutic use
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents / therapeutic use
  • Bone Neoplasms / drug therapy
  • Bone Neoplasms / genetics*
  • Bone Neoplasms / metabolism
  • Cell Line, Tumor
  • Disease-Free Survival
  • Drug Resistance, Neoplasm / genetics
  • Gene Expression / genetics
  • Genes, erbB-2
  • Humans
  • Immunohistochemistry
  • In Situ Hybridization, Fluorescence
  • Neoplasm Recurrence, Local / genetics
  • Oncogene Proteins v-erbB / metabolism
  • Osteosarcoma / drug therapy
  • Osteosarcoma / genetics*
  • Osteosarcoma / metabolism
  • Receptor, IGF Type 1 / metabolism
  • Sarcoma, Ewing / drug therapy
  • Sarcoma, Ewing / genetics*
  • Sarcoma, Ewing / metabolism
  • Trastuzumab
  • Treatment Outcome


  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents
  • Oncogene Proteins v-erbB
  • Receptor, IGF Type 1
  • Trastuzumab