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


METHODS
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 overexpression 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 not a biologically or therapeutically important pathway in ES/PNET.
Ye
Dan
D
Division of Hematology/Oncology and Simmons Cancer Center, University of Texas Southwestern Medical Center, Dallas, Texas 75390-8593, USA.
Maitra
Anirban
A
Timmons
Charles F
CF
Leavey
Patrick J
PJ
Ashfaq
Raheela
R
Ilaria
Robert L
RL
D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D015153:Blotting, Western; D001859:Bone Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D002470:Cell Survival; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007124:Immunoenzyme Techniques; D017404:In Situ Hybridization, Fluorescence; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D012512:Sarcoma, Ewing / Q000188:drug therapy / Q000378:metabolism*; D000068878:Trastuzumab; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab