Prognostic value of PAX-FKHR fusion status in alveolar rhabdomyosarcoma: a report from the cooperative soft tissue sarcoma study group (CWS).
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.


METHODS
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.
Klinikum Stuttgart, Stuttgart, Germany. s.stegmaier@klinikum-stuttgart.de
Sabine
S
Stegmaier
Christopher
C
Poremba
Karl-Ludwig
KL
Schaefer
Ivo
I
Leuschner
Bernarda
B
Kazanowska
Albert N
AN
Békássy
Stefan S
SS
Bielack
Thomas
T
Klingebiel
Ewa
E
Koscielniak
D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D002986:Clinical Trials as Topic; D005260:Female; D006801:Humans; D008297:Male; D015514:Oncogene Proteins, Fusion / Q000032:analysis*; D011237:Predictive Value of Tests; D011379:Prognosis; D012189:Retrospective Studies; D018232:Rhabdomyosarcoma, Alveolar / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D055815:Young Adult
D015514:Oncogene Proteins, Fusion; C523321:PAX3-FKHR fusion protein, human; C561715:PAX7-FKHR fusion protein, human