The epidermal growth factor receptor HER2 is not a major therapeutic target in Ewing sarcoma

Dan Ye, Anirban Maitra, Charles F. Timmons, Patrick J. Leavey, Raheela Ashfaq, Robert L. Ilaria

Research output: Contribution to journalArticle

Abstract

Background: Although chimeric EWS gene and Ets gene fusions are pathognomonic of Ewing sarcoma (ES) and primitive neuroectodermal tumors (PNET), the molecular pathogenesis of these pediatric malignancies is poorly understood. Recently, the human epidermal growth factor (HER)-2 receptor, which plays an important role in the biology of certain epithelial cancers, has been implicated in ES tumor cell line growth and chemosensitivity. Materials: To investigate whether HER2 might be a rational target for ES/PNET therapy, five ES cell lines and 13 archival primary ES/PNET samples were examined by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) for evidence of HER2 overexpression. Results: Although several ES cell lines demonstrated modest constitutive HER2 expression by immunoblot, none of the ES cell lines or primary tumor samples showed evidence of HER2 over-expression by IHC or HER2 gene amplification by FISH. Moreover, treatment of human ES cell lines with the HER2-targeted agent trastuzumab (Herceptin) had little effect on cell survival, proliferation, or growth in semi-solid medium. Conclusions: These results suggest that HER2 is nota biologically or therapeutically important pathway in ES/PNET.

Original languageEnglish (US)
Pages (from-to)459-466
Number of pages8
JournalJournal of Pediatric Hematology/Oncology
Volume25
Issue number6
DOIs
StatePublished - Jun 2003
Externally publishedYes

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Ewing's Sarcoma
Epidermal Growth Factor Receptor
Primitive Neuroectodermal Tumors
Therapeutics
Cell Line
Fluorescence In Situ Hybridization
Immunohistochemistry
erbB-2 Genes
Neoplasms
Gene Amplification
Gene Fusion
Growth
Tumor Cell Line
Cell Survival
Cell Proliferation
Pediatrics

Keywords

  • Epidermal growth factor receptor
  • Ewing sarcoma
  • EWS/FLI-1
  • HER2
  • Trastuzumab

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Oncology
  • Hematology

Cite this

The epidermal growth factor receptor HER2 is not a major therapeutic target in Ewing sarcoma. / Ye, Dan; Maitra, Anirban; Timmons, Charles F.; Leavey, Patrick J.; Ashfaq, Raheela; Ilaria, Robert L.

In: Journal of Pediatric Hematology/Oncology, Vol. 25, No. 6, 06.2003, p. 459-466.

Research output: Contribution to journalArticle

Ye, Dan ; Maitra, Anirban ; Timmons, Charles F. ; Leavey, Patrick J. ; Ashfaq, Raheela ; Ilaria, Robert L. / The epidermal growth factor receptor HER2 is not a major therapeutic target in Ewing sarcoma. In: Journal of Pediatric Hematology/Oncology. 2003 ; Vol. 25, No. 6. pp. 459-466.
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