title: Ewing sarcoma of the small bowel: a study of seven cases, including one with the uncommonly reported EWSR1-FEV translocation.
abstract: OBJECTIVE
  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.
  
  
  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.
authors.affiliation: Department of Pathology and Laboratory Medicine, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Milione
authors.forename: Patrizia
authors.initials: P
authors.lastname: Gasparini
authors.forename: Gabriella
authors.initials: G
authors.lastname: Sozzi
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Mazzaferro
authors.forename: Andrea
authors.initials: A
authors.lastname: Ferrari
authors.forename: Paolo G
authors.initials: PG
authors.lastname: Casali
authors.forename: Federica
authors.initials: F
authors.lastname: Perrone
authors.forename: Elena
authors.initials: E
authors.lastname: Tamborini
authors.forename: Alessio
authors.initials: A
authors.lastname: Pellegrinelli
authors.forename: Giorgio
authors.initials: G
authors.lastname: Gherardi
authors.forename: Gianluigi
authors.initials: G
authors.lastname: Arrigoni
authors.forename: Paola
authors.initials: P
authors.lastname: Collini
authors.forename: Adele
authors.initials: A
authors.lastname: Testi
authors.forename: Elena
authors.initials: E
authors.lastname: De Paoli
authors.forename: Antonella
authors.initials: A
authors.lastname: Aiello
authors.forename: Silvana
authors.initials: S
authors.lastname: Pilotti
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Pelosi
mesh_terms: D000293:Adolescent; D000328:Adult; D002148:Calmodulin-Binding Proteins / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D006801:Humans; D007078:Ileal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics*; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D034802:RNA-Binding Protein EWS; D016601:RNA-Binding Proteins / Q000235:genetics*; D012512:Sarcoma, Ewing / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D014157:Transcription Factors; D014178:Translocation, Genetic; D055815:Young Adult
chemical_list: D002148:Calmodulin-Binding Proteins; D004268:DNA-Binding Proteins; C500986:EWSR1 protein, human; C576197:EWSR1-FLI1 fusion protein, human; C474280:FEV protein, human; D009687:Nuclear Proteins; D015514:Oncogene Proteins, Fusion; D034802:RNA-Binding Protein EWS; D016601:RNA-Binding Proteins; D014157:Transcription Factors
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