title: Increased risk of systemic relapses associated with bone marrow micrometastasis and circulating tumor cells in localized ewing tumor.
abstract: OBJECTIVE
  The presence of metastasis is a major prognostic factor in Ewing tumor (ET). The relapse pattern of patients with localized tumors has long indicated that cases with disseminated ET cells escape detection at diagnosis. ET cells are characterized by specific gene fusions that can be detected with high sensitivity and specificity by reverse transcriptase polymerase chain reaction (RT-PCR).
  
  
  METHODS
  RT-PCR targeting EWS-FLI-1 or EWS-ERG transcripts was used to search for occult tumor cells in peripheral blood (PB) and bone marrow (BM) at diagnosis in 172 patients with ET, and the prognostic significance of this parameter was assessed.
  
  
  RESULTS
  As we suggested previously in a smaller series of patients, RT-PCR positivity of the BM was correlated with a high risk of adverse outcome in the overall study population (P =.007). More interestingly, among patients with otherwise localized tumors, BM micrometastasis also predicted significantly poorer disease-free survival rates (P =.043). The presence of circulating tumor cells (CTC) was more frequently observed in patients with large tumors (P =.006). CTC were associated with a poor outcome among patients with clinically localized disease (P =.045). Patients with clinically localized disease and peripheral occult tumor cells as evidenced by BM and/or PB RT-PCR positivity had axial or proximal tumors and experienced relapses at a systemic rather than at a local level.
  
  
  CONCLUSIONS
  Patients with localized ET and BM micrometastasis or CTC are comparable to patients with metastases in terms of the localization of the primary tumor, outcome, and relapse pattern.
authors.affiliation: Laboratoire de Pathologie Moléculaire des Cancers, INSERM U 509, Paris, France.
authors.forename: Gudrun
authors.initials: G
authors.lastname: Schleiermacher
authors.forename: Martine
authors.initials: M
authors.lastname: Peter
authors.forename: Odile
authors.initials: O
authors.lastname: Oberlin
authors.forename: Thierry
authors.initials: T
authors.lastname: Philip
authors.forename: Hervé
authors.initials: H
authors.lastname: Rubie
authors.forename: Françoise
authors.initials: F
authors.lastname: Mechinaud
authors.forename: Danièle
authors.initials: D
authors.lastname: Sommelet-Olive
authors.forename: Judith
authors.initials: J
authors.lastname: Landman-Parker
authors.forename: Danièle
authors.initials: D
authors.lastname: Bours
authors.forename: Jean
authors.initials: J
authors.lastname: Michon
authors.forename: Olivier
authors.initials: O
authors.lastname: Delattre
mesh_terms: D000293:Adolescent; D000328:Adult; D000704:Analysis of Variance; D001853:Bone Marrow / Q000473:pathology*; D001859:Bone Neoplasms / Q000401:mortality / Q000473:pathology*; D002648:Child; D002675:Child, Preschool; D018572:Disease-Free Survival; D005260:Female; D005602:France / Q000453:epidemiology; D006801:Humans; D007223:Infant; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009360:Neoplastic Cells, Circulating / Q000473:pathology*; D011379:Prognosis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012512:Sarcoma, Ewing / Q000401:mortality / Q000473:pathology*; D015996:Survival Rate