Prognostic Value of PAX-FKHR Fusion Status in Alveolar Rhabdomyosarcoma: A Report From the Cooperative Soft Tissue Sarcoma Study Group (CWS)

Research output: Contribution to journalArticle

Abstract

Background. Alveolar Rhabdomyosarcomas (RMA) are characterized by chromosomal translocations, fusing the PAX3 or PAX7 gene with FKHR in about 85%. Previous studies have suggested that the fusion type is associated with prognosis. In order to investigate the predictive value of the PAX-FKHR fusion status on disease outcome of patients with RMA treated in the CWS trials we performed a retrospective analysis. Procedure. Between 1986 and 2004, out of 446 patients with RMA treated in four consecutive CWS trials, tumor samples from 126 patients were available for RT-PCR analysis. Survival depending on fusion status in context with known clinical risk-factors was analyzed. Results. Out of 126 samples, 121 had adequate quality for PAX-FKHR fusion status analysis. PAX-FKHR fusions were detected in 101 samples: 60% PAX3-FKHR and 24% PAX7-FKHR fusions, 17% were fusion-negative. There was no significant difference in survival between patients with PAX3-FKHR versus PAX7-FKHR positive tumors. The fusion transcript negative cohort showed a more favorable outcome than the fusion transcript positive cohort among patients with metastatic disease. From the established clinical risk-factors none was associated with a significantly higher risk of failure or death in a multivariate analysis. Conclusions. PAX-FKHR fusion type was not a significant predictor for survival in our analysis. Moreextensive molecular analyses are needed to identify features with prognostic relevance and useful therapeutic impact. Pediatr Blood Cancer 2011; 57: 406-414. (C) 2011 Wiley-Liss, Inc.

Details

Authors
  • Sabine Stegmaier
  • Christopher Poremba
  • Karl-Ludwig Schaefer
  • Ivo Leuschner
  • Bernarda Kazanowska
  • Albert Békássy
  • Stefan S. Bielack
  • Thomas Klingebiel
  • Ewa Koscielniak
Organisations
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Pediatrics

Keywords

  • PAX-FKHR, prognosis, rhabdomyosarcoma, RT-PCR, translocation
Original languageEnglish
Pages (from-to)406-414
JournalPediatric Blood & Cancer
Volume57
Issue number3
Publication statusPublished - 2011
Publication categoryResearch
Peer-reviewedYes