Impact of EWS-ETS fusion type on disease progression in Ewing's sarcoma/peripheral primitive neuroectodermal tumor: prospective results from the cooperative Euro-E.W.I.N.G. 99 trial.

Abstract

PURPOSE EWS-ETS fusion genes are the driving force in Ewing's sarcoma pathogenesis. Because of the variable breakpoint locations in the involved genes, there is heterogeneity in fusion RNA and protein architecture. Since previous retrospective studies suggested prognostic differences among patients expressing different EWS-FLI1 fusion types, the impact of fusion RNA architecture on disease progression and relapse was studied prospectively within the Euro-E.W.I.N.G. 99 clinical trial. PATIENTS AND METHODS Among 1,957 patients who registered before January 1, 2007, 703 primary tumors were accessible for the molecular biology study. Fusion type was assessed by polymerase chain reaction on frozen (n = 578) or paraffin-embedded materials (n = 125). The primary end point was the time to disease progression or relapse. Results After exclusion of noninformative patients, 565 patients were entered into the prognostic factor analysis comparing type 1 (n = 296), type 2 (n = 133), nontype 1/nontype 2 EWS-FLI1 (n = 91) and EWS-ERG fusions (n = 45). Median follow-up time was 4.5 years. The distribution of sex, age, tumor volume, tumor site, disease extension, or histologic response did not differ between the four fusion type groups. We did not observe any significant prognostic value of the fusion type on the risk of progression or relapse. The only slight difference was that the risk of progression or relapse associated with nontype 1/nontype 2 EWS-FLI1 fusions was 1.38 (95% CI, 0.96 to 2.0) times higher than risk associated with other fusion types, but it was not significant (P = .10). CONCLUSION In contrast to retrospective studies, the prospective evaluation did not confirm a prognostic benefit for type 1 EWS-FLI1 fusions.

• Authors: Marie-Cecile Le Deley, Olivier Delattre, Karl-Ludwig Schaefer, Sue A Burchill, Gabriele Koehler, Pancras C W Hogendoorn, Thomas Lion, Christopher Poremba, Julien Marandet, Stelly Ballet, Gaelle Pierron, Samantha C Brownhill, Michaela Nesslböck, Andreas Ranft, Uta Dirksen, Odile Oberlin, Ian J Lewis, Alan W Craft, Heribert Jürgens, Heinrich Kovar
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 28 Issue 12 Pg. 1982-8 (Apr 20 2010) ISSN: 1527-7755 [Electronic] United States
• PMID: 20308673 (Publication Type: Comparative Study, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)

Chemical References

• EWS-ERG fusion protein, human
• EWS-FLI fusion protein
• Oncogene Proteins, Fusion
• Proto-Oncogene Protein c-fli-1
• RNA-Binding Protein EWS
• Transcription Factors

Topics

• Adult
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Biopsy
• Bone Neoplasms (genetics, mortality, pathology, therapy)
• Chi-Square Distribution
• Disease Progression
• Europe
• Female
• Gene Expression Regulation, Neoplastic
• Genetic Predisposition to Disease
• Humans
• Kaplan-Meier Estimate
• Male
• Neoplasm Recurrence, Local
• Oncogene Proteins, Fusion (genetics)
• Paraffin Embedding
• Phenotype
• Proportional Hazards Models
• Prospective Studies
• Proto-Oncogene Protein c-fli-1 (genetics)
• RNA-Binding Protein EWS
• Radiotherapy, Adjuvant
• Reverse Transcriptase Polymerase Chain Reaction
• Risk Assessment
• Risk Factors
• Sarcoma, Ewing (genetics, mortality, secondary, therapy)
• Stem Cell Transplantation
• Time Factors
• Transcription Factors (genetics)
• Treatment Outcome
• Young Adult