title: Catecholamines profiles at diagnosis: Increased diagnostic sensitivity and correlation with biological and clinical features in neuroblastoma patients.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  Our study demonstrates that analysis of a urinary catecholamine metabolite panel, comprising 8 metabolites, ensures the highest sensitivity to diagnose NBL patients.
authors.affiliation: 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.
authors.forename: Iedan R N
authors.initials: IR
authors.lastname: Verly
authors.affiliation: Laboratory Genetic Metabolic Diseases, Emma Children's Hospital/Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands.
authors.forename: André B P
authors.initials: AB
authors.lastname: van Kuilenburg
authors.affiliation: Laboratory Genetic Metabolic Diseases, Emma Children's Hospital/Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands.
authors.forename: Nico G G M
authors.initials: NG
authors.lastname: Abeling
authors.affiliation: Laboratory Genetic Metabolic Diseases, Emma Children's Hospital/Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands.
authors.forename: Susan M I
authors.initials: SM
authors.lastname: Goorden
authors.affiliation: 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.
authors.forename: Marta
authors.initials: M
authors.lastname: Fiocco
authors.affiliation: Laboratory Genetic Metabolic Diseases, Emma Children's Hospital/Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands.
authors.forename: Frédéric M
authors.initials: FM
authors.lastname: Vaz
authors.affiliation: 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.
authors.forename: Max M
authors.initials: MM
authors.lastname: van Noesel
authors.affiliation: Department of Pediatric Oncology/Hematology, Sophia Children's Hospital/Erasmus Medical Center, Wytemaweg 80, 3015 CN Rotterdam, The Netherlands.
authors.forename: C Michel
authors.initials: CM
authors.lastname: Zwaan
authors.affiliation: Department of Pediatric Oncology/Hematology, VU University Medical Center, De Boelelaan 1118, 1081 HZ Amsterdam, The Netherlands.
authors.forename: GertJan L
authors.initials: GL
authors.lastname: Kaspers
authors.affiliation: Department of Pediatric Oncology/Hematology, Emma Children's Hospital/Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands.
authors.forename: Johannes H M
authors.initials: JH
authors.lastname: Merks
authors.affiliation: Department of Pediatric Oncology/Hematology, Emma Children's Hospital/Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands.
authors.forename: Huib N
authors.initials: HN
authors.lastname: Caron
authors.affiliation: 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.
authors.forename: Godelieve A M
authors.initials: GA
authors.lastname: Tytgat
mesh_terms: D000293:Adolescent; D014408:Biomarkers, Tumor / Q000652:urine*; D002395:Catecholamines / Q000378:metabolism / Q000652:urine*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D009447:Neuroblastoma / Q000652:urine*; D012189:Retrospective Studies; D012680:Sensitivity and Specificity
chemical_list: D014408:Biomarkers, Tumor; D002395:Catecholamines
keywords: Catecholamines; Diagnostic sensitivity; MIBG non-avid tumours; Neuroblastoma; VMA and HVA negative