Detection of the PAX3-FKHR fusion gene in paediatric rhabdomyosarcoma: a reproducible predictor of outcome?

Rhabdomyosarcoma has 2 major histological subtypes, embryonal and alveolar. Alveolar histology is associated with the fusion genes PAX3-FKHR and PAX7- FKHR. Definition of alveolar has been complicated by changes in terminology and subjectivity. It is currently unclear whether adverse clinical behavio ur is better predicted by the presence of these fusion genes or by alveolar histology. We have determined the presence of the PAX3/7-FKHR fusion genes in 91 primary rhabdomyosarcoma tumours using a combination of classical cy togenetics, FISH and RT-PCR, with a view to determining the clinical charac teristics of tumours with and without the characteristic translocations. Th ere were 37 patients with t(2;13)/PAX3-FKHR, 8 with t(1;13) PAX7-FKHR and 4 6 with neither translocation. One or other of the characteristic translocat ions was found in 31/38 (82%) of alveolar cases. Univariate survival analys is revealed the presence of the translocation t(2;13)/PAX3-FKHR to be an ad verse prognostic factor. With the difficulties in morphological diagnosis o f alveolar rhabdomyosarcoma on increasingly used small needle biopsy specim ens, these data suggest that molecular analysis for PAX3-FKHR will be a cli nically useful tool in treatment stratification in the future. This hypothe sis requires testing in a prospective study. Variant t(1;13)/PAX7-FKHR appe ars biologically different, occurring in younger patients with more localis ed disease. (C) 2001 Cancer Research Campaign.