Catecholamines profiles at diagnosis: Increased diagnostic sensitivity and correlation with biological and clinical features in neuroblastoma patients

Iedan R N Verly, André B P van Kuilenburg, Nico G G M Abeling, Susan M I Goorden, Marta Fiocco, Frédéric M Vaz, Max M van Noesel, C Michel Zwaan, GertJan L Kaspers, Johannes H M Merks, Huib N Caron, Godelieve A M Tytgat

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

INTRODUCTION: Neuroblastoma (NBL) accounts for 10% of the paediatric malignancies and is responsible for 15% of the paediatric cancer-related deaths. Vanillylmandelic acid (VMA) and homovanillic acid (HVA) are most commonly analysed in urine of NBL patients. However, their diagnostic sensitivity is suboptimal (82%). Therefore, we performed in-depth analysis of the diagnostic sensitivity of a panel of urinary catecholamine metabolites.

PATIENTS AND METHODS: Retrospective study of a panel of 8 urinary catecholamine metabolites (VMA, HVA, 3-methoxytyramine [3MT], dopamine, epinephrine, metanephrine, norepinephrine and normetanephrine [NMN]) from 301 NBL patients at diagnosis. Special attention was given to subgroups, metaiodobenzylguanidine (MIBG) non-avid tumours and VMA/HVA negative patients.

RESULTS: Elevated catecholamine metabolites, especially 3MT, correlated with nine out of 12 NBL characteristics such as stage, age, MYCN amplification, loss of heterozygosity for 1p and bone-marrow invasion. The combination of the classical markers VMA and HVA had a diagnostic sensitivity of 84%. NMN was the most sensitive single diagnostic metabolite with overall sensitivity of 89%. When all 8 metabolites were combined, a diagnostic sensitivity of 95% was achieved. Among the VMA and HVA negative patients, were also 29% with stage 4 disease, which usually had elevation of other catecholamine metabolites (93%). Diagnostic sensitivity for patients with MIBG non-avid tumour was improved from 33% (VMA and/or HVA) to 89% by measuring the panel.

CONCLUSIONS: Our study demonstrates that analysis of a urinary catecholamine metabolite panel, comprising 8 metabolites, ensures the highest sensitivity to diagnose NBL patients.

Original languageEnglish
Pages (from-to)235-243
Number of pages9
JournalEuropean Journal of Cancer
Volume72
DOIs
Publication statusPublished - Feb 2017

Cite this

Verly, I. R. N., van Kuilenburg, A. B. P., Abeling, N. G. G. M., Goorden, S. M. I., Fiocco, M., Vaz, F. M., ... Tytgat, G. A. M. (2017). Catecholamines profiles at diagnosis: Increased diagnostic sensitivity and correlation with biological and clinical features in neuroblastoma patients. European Journal of Cancer, 72, 235-243. https://doi.org/10.1016/j.ejca.2016.12.002