Flow cytometric DNA content helps predicting recurrence in children with neuroblastoma

Aim of the study was to evaluate the prognostic value of DNA index (DI), S-phase fraction (SPF) and N-myc amplification in children with neuroblastoma, using fresh or frozen samples obtained at diagnosis. The study includes 123 children with a mean age of 26 months followed-up for a mean time of 37 months to evaluate the overall survival (OS) and the event-free survival (EFS). Death and recurrence incidences were respectively 15% (18 cases) and 25% (30 cases). DNA aneuploidy (DI not equal I)incidence was 85/123 (69%) while median SPF was 6.1%. N-myc amplification was detected in 17/119 cases (14%) of which 15 corresponded to stage 4 tumors. Univariate analysis showed that OS probability was significantly correlated with stage (p = 0.0001), age (p = 0.0002), DI (p = 0.002) and, at lesser degree, with N-myc (p = 0.04). In particular, for the subgroup of children with stage 4, OS was only slightly influenced by DT (p = 0.02). Univariate probability EFS for the prediction of recurrence (excluding stage 4s cases) was found to be high in children with tumours having DNA diploid (p = 0.001) and stage 4 (p = 0.001). SPF values were not useful to predict neither OS nor EFS. Multivariate analysis was performed for both OS and EFS data: stage and age but not DI were relevant (p < 0.01) for predicting OS, while DI and stage but not age were relevant for predicting recurrence (EFS). In conclusion, the present study indicates that flow cytometric DNA diploidy is an important prognostic factor of recurrence in children with neuroblastoma.