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Clin Biochem. 2014 Jun;47(9):848-52. doi: 10.1016/j.clinbiochem.2014.04.015. Epub 2014 Apr 21.

Urinary homovanillic and vanillylmandelic acid in the diagnosis of neuroblastoma: report from the Italian Cooperative Group for Neuroblastoma.

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Clinical Pathology Laboratory Unit, Istituto Giannina Gaslini, Genoa, Italy.
Department of Biostatistics, Mediservice s.r.l., World Trade Center, Via De Marini 1, Genoa, Italy.
Department of Hematology-Oncology, Istituto Giannina Gaslini, Genoa, Italy.
Department of Pediatric Hematology-Oncology, University of Padova Italy.
Department of Pediatric Oncology Azienda Ospedale Policlinico di Bari, Italy.
Division of Pediatric Hematology and Oncology, Department of Hematology, Santo Spirito Hospital, Pescara, Italy.
Clinical Pathology Laboratory Unit, Istituto Giannina Gaslini, Genoa, Italy. Electronic address:



Urinary homovanillic and vanillylmandelic acid (HVA and VMA) are well known biomarkers for the management of neuroblastoma (NB). Very few and contradictory publications on their diagnostic performance are present in the literature. The aim of this study is to review the results of HVA/Cr and VMA/Cr obtained by the reference laboratory of the Italian Cooperative Group for NB within a 7-year period using HPLC-EC.


Updated reference intervals based on age as a continuous variable were calculated by using a multivariate statistical analysis. The diagnostic performance of the two biomarkers has been established by calculating their specificity and sensitivity and by receiver operating characteristics (ROC) curves for different ages and stages of disease.


Accurate age-related reference intervals were obtained from 648 HVA/Cr and 671 VMA/Cr results derived from patients in which the diagnosis of neuroendocrine tumors was excluded. Sensitivity, specificity and ROC curves were obtained from 169 HVA/Cr and 179 VMA/Cr results from confirmed NB patients. The best diagnostic performance was obtained in stage 4S tumors and in children <18months.


This is the first report, to our knowledge, that analyzes in depth the diagnostic performance of HVA/Cr and VMA/Cr for NB in different stages and age subgroups. In addition, the present work provides cut-off points able to discriminate between NB patients and negative subjects suspected to have NB and could be of help in taking medical decisions.


Homovanillic acid; Neuroblastoma; ROC curve; Reference values; Vanillylmandelic acid

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