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

Katia Scotlandi, Maria C. Manara, Claudia M. Hattinger, Stefania Benini, Stefania Perdichizzi, Michela Pasello, Gaetano Bacci, Licciana Zanella, Franco Bertoni, Piero Picci, Massimo Serra

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)1349-1361
Number of pages13
JournalEuropean Journal of Cancer
Volume41
Issue number9
DOIs
Publication statusPublished - Jun 2005

Keywords

  • Ewing's sarcoma
  • HER2
  • IGF-IR
  • Osteosarcoma
  • P-glycoprotein
  • Trastuzumab

ASJC Scopus subject areas

  • Cancer Research
  • Hematology
  • Oncology

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