Sebastiano Barco1, Iedan Verly2, Maria Valeria Corrias3, Stefania Sorrentino4, Massimo Conte4, Gino Tripodi1, Godelieve Tytgat5, André van Kuilenburg6, Maria van der Ham7, Monique de Sain-van der Velden7, Alberto Garaventa4, Giuliana Cangemi8. 1. Central Laboratory of Analyses, IRCCS Istituto Giannina Gaslini, Genoa, Italy. 2. Department of Pediatric Oncology, Amsterdam UMC, Amsterdam, the Netherlands; Princess Maxima Center for Pediatric Oncology, Utrecht, the Netherlands; Laboratory of Genetic Metabolic Disorders, Amsterdam UMC, Amsterdam, the Netherlands. 3. Laboratory of experimental therapies in oncology, IRCCS Istituto Giannina Gaslini, Genoa, Italy. 4. Department of Pediatric oncology, IRCCS Istituto Giannina Gaslini, Genoa, Italy. 5. Department of Pediatric Oncology, Amsterdam UMC, Amsterdam, the Netherlands; Princess Maxima Center for Pediatric Oncology, Utrecht, the Netherlands. 6. Laboratory of Genetic Metabolic Disorders, Amsterdam UMC, Amsterdam, the Netherlands. 7. Department of Genetics, Section Metabolic Diagnostics, WKZ, Utrecht, the Netherlands. 8. Central Laboratory of Analyses, IRCCS Istituto Giannina Gaslini, Genoa, Italy. Electronic address: giulianacangemi@gaslini.org.
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.
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.