Plasma free metanephrines for diagnosis of neuroblastoma patients

Sebastiano Barco, Iedan Verly, Maria Valeria Corrias, Stefania Sorrentino, Massimo Conte, Gino Tripodi, Godelieve Tytgat, André van Kuilenburg, Maria van der Ham, Monique de Sain-van der Velden, Alberto Garaventa, Giuliana Cangemi

Research output: Contribution to journalArticle

Abstract

INTRODUCTION: A substantial number of patients with neuroblastoma (NB) have increased excretion of catecholamines and metanephrines. Here, we have investigated the diagnostic role of plasma free metanephrines (PFM), metanephrine (MN), normetanephrine (NMN) and 3-methoxytyramine (3MT) for NB, the most common extra-cranial solid tumour in children.

METHODS: PFM were quantified by using a commercial IVD-CE LC-MS/MS method on a TSQ Quantiva coupled to an Ultimate 3000. The method was further validated on 103 samples from pediatric subjects (54 patients with histologically confirmed NB and 49 age and sex matched controls). Correlations between PFM concentrations with clinical factors were tested. We directly compared MN, NMN, and 3MT concentrations in matched plasma and urine samples of NB patients (n = 29).

RESULTS: 3MT and NMN showed an excellent diagnostic performance with very high specificity (100% and 95.8%, respectively) and sensitivity (88.2% and 80.4%). ROC curves were obtained (AUC of 0.93 and 0.91 for 3MT and NMN, respectively) and optimal cut-offs that could discriminate between controls and NB patients were defined. A positive correlation between NMN levels in urine and plasma (p = .0017) was found.

DISCUSSION: The determination of plasma 3MT and NMN should be taken in consideration as a new diagnostic tool for NB. Validation in prospective clinical studies in comparison to urinary catecholamines and metanephrines is warranted.

Original languageEnglish
Pages (from-to)57-62
Number of pages6
JournalClinical Biochemistry
Volume66
DOIs
Publication statusPublished - Apr 2019

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Keywords

  • Child
  • Child, Preschool
  • Chromatography/methods
  • Cohort Studies
  • Dopamine/analogs & derivatives
  • Female
  • Humans
  • Infant
  • Infant, Newborn
  • Male
  • Metanephrine/analysis
  • Neuroblastoma/diagnosis
  • Normetanephrine/analysis
  • ROC Curve

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