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
N1 - Publisher Copyright:
© 2019 The Canadian Society of Clinical Chemists
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 - Diagnosis
KW - Liquid chromatography-tandem mass spectrometry
KW - Neuroblastoma
KW - Plasma free metanephrines
UR - http://www.scopus.com/inward/record.url?scp=85062079192&partnerID=8YFLogxK
U2 - 10.1016/j.clinbiochem.2019.02.012
DO - 10.1016/j.clinbiochem.2019.02.012
M3 - Article
C2 - 30822416
AN - SCOPUS:85062079192
SN - 0009-9120
VL - 66
SP - 57
EP - 62
JO - Clinical Biochemistry
JF - Clinical Biochemistry
ER -