The prognostic role of urinary catecholamines in infants with disseminated neuroblastoma may be mediated by MYCN amplification

To the Editor: In their recent article, Strenger et al. [1] evaluated the diagnostic and prognostic role of urinary catecholamines in relation to stage, age at diagnosis, and biological characteristics in 114 NB patients. The Authors pointed out that low values of urinary VMA and of VMA/HVA ratio, or high values of DA/VMA and of DA/HVA ratios, may be predictive of a poor prognosis in aggressive NB, being associated with MYCN amplification, 1p deletion and other unfavorable characteristics. Moreover, the Authors suggested that urinary catecholamines might be useful to better differentiate stage 4 from stage 4s in infants. They did not evaluate the prognostic role of these markers in such two groups, probably due to the small sample size in their cohort (14 patients in stage 4s, whose only one died during the follow-up period; data for stage 4 infants were not provided). At this regard, a retrospective study, based on data of the Italian Neuroblastoma Registry (INR), is currently in progress at the Gaslini Children’s Hospital of Genoa (Italy) to evaluate the diagnostic and prognostic characteristics of 100 infants with disseminated NB (32 stage 4 and 68 stage 4s), diagnosed between 1991 and 1999 and followed up to December 2004. VMA urinary levels were available for 87 patients, of which 64 (74%) had also valid data for MYCN status. Data on urinary HVA levels and 1p deletion were not evaluable due to the high proportion of missing data (about 50% in both groups), while data on urinary DA concentrations were not available from INR. Similar to Strenger et al. we observedhigherVMA levels in stage 4s than in stage 4 patients (sensitivity1⁄4 86% vs. 67%, P1⁄4 0.035, w test). Moreover, the association between low VMA levels and MYCN amplification was confirmed (P1⁄4 0.015). However, after stratification by stage, this association was more evident in stage 4 (56% of MYCN amplified vs. 13%, P1⁄4 0.054) than in stage 4s infants (17% vs. 9%, P1⁄4 0.502). The large size of our population allowed us to estimate the 5-year overall survival (OS) by stage and MYCN amplification. In this analysis, stage 4 infants with high VMA levels had the better OS as compared to those with VMA within the normal range (90% vs. 40%, P1⁄4 0.002, log-rank test). Interestingly, when the analysis was stratified by MYCN status, the effect was evident only for those without MYCN amplification (OS1⁄4 100% vs. 50%,P1⁄4 0.0045). In stage 4s patients we could not find any effect of VMA status on survival, regardless on MYCN status, even if the low proportion of MYCN amplified in this group (n1⁄4 4) prevent to draw definitive conclusions. Our results confirm that urinary cathecolamines may be successfully employed for the diagnosis of stage 4s NB and suggest that they might be used as prognostic markers in stage 4 infants withoutMYCN amplification. In agreement with Strenger et al., our observations indicate that urinary cathecolamines may play different prognostic and diagnostic roles in relation with clinical and biological characteristics of the tumor. As a consequence, a comprehensive approach, taking into account the complex interdependency between biological and clinical features, should be applied to large cohorts of patients, to elucidate the impact of urinary catecholamines (and possibly other newly discovered markers), in the diagnosis and prognosis of NB.