Ewing sarcoma of the small bowel: a study of seven cases, including one with the uncommonly reported EWSR1-FEV translocation

Histopathology. 2014 Jun;64(7):1014-26. doi: 10.1111/his.12350. Epub 2014 Feb 25.

Abstract

Aims: Primary Ewing sarcoma of the ileum has rarely been documented. Little is known about its pathogenesis and clinical implications, and it would be helpful to identify novel molecular markers. EWSR1-FEV translocation is exceedingly rare in Ewing sarcoma, as FEV expression is restricted to prostate, brain and serotonin neuroendocrine cells (NE) and related tumours.

Methods and results: Paraffin sections or snap-frozen material were used in this investigation. Tumours were investigated by means of immunohistochemistry, RT-PCR (EWSR1-FLI1, EWSR1-ERG and EWSR1-FEV transcripts), FISH analysis (EWSR1 break-apart and specific EWSR1-FEV translocation) and spectral karyotyping (SKY). Ten ileal neuroendocrine tumours (INET) made up the control group for EWSR1-FEV translocation. Among 445 Ewing sarcomas cases spanning a period of 20 years, seven (1.6%) arose in the ileum. All tumours were immunoreactive for synaptophysin, CD99, FLI1 and vimentin. FISH identified EWSR1 rearrangement in all cases, with EWSR1-FLI1 transcripts being detected in all but one tumour showing the uncommon EWSR1-FEV rearrangement, with SKY, RT-PCR and FISH confirmation. The mean survival of EWSR1-FLI1 patients was 14 months, whereas the EWSR1-FEV patient was alive after 15 years despite several recurrences controlled by surgery alone. No INET showed EWSR1 translocation.

Conclusions: Most primary Ewing sarcomas of the ileum show the common EWSR1-FLI1 translocation, but EWSR1-FEV could be specific for tumours arising in the ileum and showing better prognosis.

Keywords: EWSR1-FEV fusion gene; EWSR1-FLI1 fusion gene; Ewing sarcoma; cytogenetic assay; fluorescence in-situ hybridization; gastrointestinal stromal tumour; ileum; immunohistochemistry; neuroectodermal; neuroendocrine; reverse transcriptase-polymerase chain reaction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Calmodulin-Binding Proteins / genetics*
  • DNA-Binding Proteins / genetics*
  • Female
  • Humans
  • Ileal Neoplasms / genetics
  • Ileal Neoplasms / metabolism
  • Ileal Neoplasms / pathology*
  • Immunohistochemistry
  • In Situ Hybridization, Fluorescence
  • Male
  • Middle Aged
  • Nuclear Proteins / genetics*
  • Oncogene Proteins, Fusion / genetics*
  • RNA-Binding Protein EWS
  • RNA-Binding Proteins / genetics*
  • Sarcoma, Ewing / genetics
  • Sarcoma, Ewing / metabolism
  • Sarcoma, Ewing / pathology*
  • Transcription Factors
  • Translocation, Genetic
  • Young Adult

Substances

  • Calmodulin-Binding Proteins
  • DNA-Binding Proteins
  • EWSR1 protein, human
  • EWSR1-FLI1 fusion protein, human
  • FEV protein, human
  • Nuclear Proteins
  • Oncogene Proteins, Fusion
  • RNA-Binding Protein EWS
  • RNA-Binding Proteins
  • Transcription Factors