Ewing tumor: tumor biology and clinical applications

Int J Surg Pathol. 2001 Jan;9(1):7-17. doi: 10.1177/106689690100900104.


The Ewing tumor family includes classical Ewing's sarcoma of bone and soft tissues, peripheral primitive neuroectodermal tumors (pPNET), Askin tumor, and other less frequent variants. This group of tumors is defined by the consistent presence of chromosomal translocations resulting in gene fusions between EWS gene and a member of the ETS family of transcription factors, mainly FLI1 and ERG. Analogous fusions are seen in other solid developmental tumors, like desmoplastic small round cell tumor. These fusions, which are consistently present and tumor-specific, control transcription of several target genes, largely unknown but critical to cell proliferation and differentiation. Therefore, gene fusions are useful to diagnose and classify small round cell tumors, have prognostic significance, are probably useful to detect micrometastasis and monitor minimal residual disease, and are potential therapeutic targets. Secondary molecular alterations, which include mutations of cell cycle regulatory genes, are not tumor-specific but are related to progression and may have prognostic value. The Ewing tumor family represents a paradigm of the application of the knowledge of biology of neoplasia to the clinical management of patients.

Publication types

  • Review

MeSH terms

  • Artificial Gene Fusion
  • Bone Neoplasms / classification
  • Bone Neoplasms / genetics
  • Bone Neoplasms / pathology*
  • Cation Transport Proteins*
  • DNA-Binding Proteins / genetics
  • ERG1 Potassium Channel
  • Ether-A-Go-Go Potassium Channels
  • Heterogeneous-Nuclear Ribonucleoproteins
  • Humans
  • Neuroectodermal Tumors, Primitive, Peripheral / classification
  • Neuroectodermal Tumors, Primitive, Peripheral / genetics
  • Neuroectodermal Tumors, Primitive, Peripheral / pathology*
  • Potassium Channels / genetics
  • Potassium Channels, Voltage-Gated*
  • Prognosis
  • Proto-Oncogene Protein c-fli-1
  • Proto-Oncogene Proteins*
  • RNA-Binding Protein EWS
  • Recombinant Fusion Proteins / genetics
  • Ribonucleoproteins / genetics
  • Sarcoma, Ewing / classification
  • Sarcoma, Ewing / genetics
  • Sarcoma, Ewing / pathology*
  • Soft Tissue Neoplasms / classification
  • Soft Tissue Neoplasms / genetics
  • Soft Tissue Neoplasms / pathology*
  • Trans-Activators / genetics
  • Transcriptional Regulator ERG
  • Translocation, Genetic


  • Cation Transport Proteins
  • DNA-Binding Proteins
  • ERG protein, human
  • ERG1 Potassium Channel
  • Ether-A-Go-Go Potassium Channels
  • Heterogeneous-Nuclear Ribonucleoproteins
  • KCNH6 protein, human
  • Potassium Channels
  • Potassium Channels, Voltage-Gated
  • Proto-Oncogene Protein c-fli-1
  • Proto-Oncogene Proteins
  • RNA-Binding Protein EWS
  • Recombinant Fusion Proteins
  • Ribonucleoproteins
  • Trans-Activators
  • Transcriptional Regulator ERG