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

doi:https://doi.org/10.1016/j.clinbiochem.2019.02.012

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 journal › Article › Academic › peer-review

14 Citations (Scopus)

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 language	English
Pages (from-to)	57-62
Number of pages	6
Journal	Clinical Biochemistry
Volume	66
DOIs	https://doi.org/10.1016/j.clinbiochem.2019.02.012
Publication status	Published - Apr 2019

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

Access to Document

https://doi.org/10.1016/j.clinbiochem.2019.02.012

Cite this

@article{5975e134dec949f2a5fdcfd5ed576735,

title = "Plasma free metanephrines for diagnosis of neuroblastoma patients",

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.",

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",

author = "Sebastiano Barco and Iedan Verly and Corrias, {Maria Valeria} and Stefania Sorrentino and Massimo Conte and Gino Tripodi and Godelieve Tytgat and {van Kuilenburg}, Andr{\'e} and {van der Ham}, Maria and {de Sain-van der Velden}, Monique and Alberto Garaventa and Giuliana Cangemi",

year = "2019",

month = apr,

doi = "https://doi.org/10.1016/j.clinbiochem.2019.02.012",

language = "English",

volume = "66",

pages = "57--62",

journal = "Clinical Biochemistry",

issn = "0009-9120",

publisher = "Elsevier Inc.",

}

TY - JOUR

T1 - Plasma free metanephrines for diagnosis of neuroblastoma patients

AU - Barco, Sebastiano

AU - Verly, Iedan

AU - Corrias, Maria Valeria

AU - Sorrentino, Stefania

AU - Conte, Massimo

AU - Tripodi, Gino

AU - Tytgat, Godelieve

AU - van Kuilenburg, André

AU - van der Ham, Maria

AU - de Sain-van der Velden, Monique

AU - Garaventa, Alberto

AU - Cangemi, Giuliana

PY - 2019/4

Y1 - 2019/4

N2 - 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.

AB - 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.

KW - Child

KW - Child, Preschool

KW - Chromatography/methods

KW - Cohort Studies

KW - Dopamine/analogs & derivatives

KW - Female

KW - Humans

KW - Infant

KW - Infant, Newborn

KW - Male

KW - Metanephrine/analysis

KW - Neuroblastoma/diagnosis

KW - Normetanephrine/analysis

KW - ROC Curve

U2 - https://doi.org/10.1016/j.clinbiochem.2019.02.012

DO - https://doi.org/10.1016/j.clinbiochem.2019.02.012

M3 - Article

C2 - 30822416

SN - 0009-9120

VL - 66

SP - 57

EP - 62

JO - Clinical Biochemistry

JF - Clinical Biochemistry

ER -