title: Clinical validation of urine 3-methoxytyramine as a biomarker of neuroblastoma and comparison with other catecholamine-related biomarkers.
abstract: Background Urinary dopamine, homovanillic acid and 4-hydroxy-3-methoxymandelic acid are established tests for diagnosis and monitoring of neuroblastic disease. We compared the diagnostic performance of total urinary 3-methoxytyramine, the O-methylated product of dopamine, to these three established tumour markers. Methods Urinary 3-methoxytyramine, dopamine, homovanillic acid and 4-hydroxy-3-methoxymandelic acid were measured by high-performance liquid chromatography with electrochemical detection on consecutive urine samples from histologically proven neuroblastic patients and controls. Patients with neuroblastic disease were further classified as untreated, advancing, residual or absent disease based on clinical and radiological criteria. Receiver operating characteristic curve analysis was used to compare the diagnostic performance of the four tumour markers. Results Urinary 3-methoxytyramine was well correlated with established tumour markers and its concentration correlated with disease activity. It was the most commonly elevated tumour marker in neuroblastic disease and showed similar sensitivity to dopamine and homovanillic acid. The diagnostic utility of urinary 3-methoxytyramine as measured by area under the receiver operating characteristic curve was similar to dopamine and homovanillic acid. Conclusion Our results support the use of urinary 3-methoxytyramine as a tumour marker in the diagnosis and the monitoring of neuroblastoma disease.
authors.affiliation: 1 Department of Chemical Pathology, Labplus, Auckland City Hospital, Auckland, New Zealand.
authors.forename: Leo
authors.initials: L
authors.lastname: Lam
authors.affiliation: 1 Department of Chemical Pathology, Labplus, Auckland City Hospital, Auckland, New Zealand.
authors.forename: Gerald A
authors.initials: GA
authors.lastname: Woollard
authors.affiliation: 2 Department of Paediatric Oncology, Starship Hospital, Auckland, New Zealand.
authors.forename: Lochie
authors.initials: L
authors.lastname: Teague
authors.affiliation: 1 Department of Chemical Pathology, Labplus, Auckland City Hospital, Auckland, New Zealand.
authors.forename: James S
authors.initials: JS
authors.lastname: Davidson
mesh_terms: D014408:Biomarkers, Tumor / Q000652:urine*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D002851:Chromatography, High Pressure Liquid; D004298:Dopamine / Q000031:analogs & derivatives* / Q000652:urine; D005260:Female; D006719:Homovanillic Acid / Q000652:urine; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008676:Metanephrine / Q000652:urine; D009367:Neoplasm Staging; D018365:Neoplasm, Residual; D009423:Nervous System Neoplasms / Q000175:diagnosis* / Q000473:pathology / Q000652:urine*; D009447:Neuroblastoma / Q000175:diagnosis* / Q000473:pathology / Q000652:urine*; D012372:ROC Curve; D013564:Sympathetic Nervous System / Q000378:metabolism / Q000473:pathology; D014642:Vanilmandelic Acid / Q000652:urine
chemical_list: D014408:Biomarkers, Tumor; D008676:Metanephrine; D014642:Vanilmandelic Acid; C001746:3-methoxytyramine; D004298:Dopamine; D006719:Homovanillic Acid
keywords: 3-methoxytyramine; Neuroblastoma; biological tumour markers; dopamine; sensitivity and specificity