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. More extensive molecular analyses are needed to identify features with prognostic relevance and useful therapeutic impact.
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. More extensive molecular analyses are needed to identify features with prognostic relevance and useful therapeutic impact.
Authors: Pooja Hingorani; Edoardo Missiaglia; Janet Shipley; James R Anderson; Timothy J Triche; Mauro Delorenzi; Julie Gastier-Foster; Michele Wing; Douglas S Hawkins; Stephen X Skapek Journal: Clin Cancer Res Date: 2015-10-15 Impact factor: 12.531
Authors: Stephen X Skapek; James Anderson; Frederic G Barr; Julia A Bridge; Julie M Gastier-Foster; David M Parham; Erin R Rudzinski; Timothy Triche; Douglas S Hawkins Journal: Pediatr Blood Cancer Date: 2013-03-22 Impact factor: 3.167
Authors: Katja Simon-Keller; Annette Paschen; Andreas A Hombach; Philipp Ströbel; Jean-Michel Coindre; Stefan B Eichmüller; Angela Vincent; Stefan Gattenlöhner; Florian Hoppe; Ivo Leuschner; Sabine Stegmaier; Ewa Koscielniak; Martin Leverkus; Dario C Altieri; Hinrich Abken; Alexander Marx Journal: Am J Pathol Date: 2013-04-02 Impact factor: 4.307