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Eur J Cancer. 2017 Feb;72:235-243. doi: 10.1016/j.ejca.2016.12.002. Epub 2017 Jan 4.

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

Author information

1
Department of Pediatric Oncology/Hematology, Emma Children's Hospital/Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands; Laboratory Genetic Metabolic Diseases, Emma Children's Hospital/Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands; Princess Máxima Center for Pediatric Oncology/Hematology, Lundlaan 6, 3584 EA Utrecht, The Netherlands.
2
Laboratory Genetic Metabolic Diseases, Emma Children's Hospital/Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands.
3
Department of Medical Statistics and Bioinformatics, Leiden University Medical Center, Eindhovenweg 20, 2333 ZC Leiden, The Netherlands; Mathematical Institute, Leiden University, Niels Bohrweg 1, 2333 CA Leiden, The Netherlands.
4
Princess Máxima Center for Pediatric Oncology/Hematology, Lundlaan 6, 3584 EA Utrecht, The Netherlands; University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands.
5
Department of Pediatric Oncology/Hematology, Sophia Children's Hospital/Erasmus Medical Center, Wytemaweg 80, 3015 CN Rotterdam, The Netherlands.
6
Department of Pediatric Oncology/Hematology, VU University Medical Center, De Boelelaan 1118, 1081 HZ Amsterdam, The Netherlands.
7
Department of Pediatric Oncology/Hematology, Emma Children's Hospital/Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands.
8
Department of Pediatric Oncology/Hematology, Emma Children's Hospital/Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands; Princess Máxima Center for Pediatric Oncology/Hematology, Lundlaan 6, 3584 EA Utrecht, The Netherlands. Electronic address: G.A.M.Tytgat@prinsesmaximacentrum.nl.

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.

KEYWORDS:

Catecholamines; Diagnostic sensitivity; MIBG non-avid tumours; Neuroblastoma; VMA and HVA negative

PMID:
28061374
DOI:
10.1016/j.ejca.2016.12.002
[Indexed for MEDLINE]

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