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


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Clinical Pathology Laboratory Unit, Istituto Giannina Gaslini, Genoa, Italy.
Sebastiano
S
Barco
Clinical Pathology Laboratory Unit, Istituto Giannina Gaslini, Genoa, Italy.
Iulian
I
Gennai
Department of Biostatistics, Mediservice s.r.l., World Trade Center, Via De Marini 1, Genoa, Italy.
Giorgio
G
Reggiardo
Department of Hematology-Oncology, Istituto Giannina Gaslini, Genoa, Italy.
Barbara
B
Galleni
Clinical Pathology Laboratory Unit, Istituto Giannina Gaslini, Genoa, Italy.
Laura
L
Barbagallo
Clinical Pathology Laboratory Unit, Istituto Giannina Gaslini, Genoa, Italy.
Angelo
A
Maffia
Department of Pediatric Hematology-Oncology, University of Padova Italy.
Elisabetta
E
Viscardi
Department of Pediatric Oncology Azienda Ospedale Policlinico di Bari, Italy.
Francesco
F
De Leonardis
Division of Pediatric Hematology and Oncology, Department of Hematology, Santo Spirito Hospital, Pescara, Italy.
Valerio
V
Cecinati
Department of Hematology-Oncology, Istituto Giannina Gaslini, Genoa, Italy.
Stefania
S
Sorrentino
Department of Hematology-Oncology, Istituto Giannina Gaslini, Genoa, Italy.
Alberto
A
Garaventa
Department of Hematology-Oncology, Istituto Giannina Gaslini, Genoa, Italy.
Massimo
M
Conte
Clinical Pathology Laboratory Unit, Istituto Giannina Gaslini, Genoa, Italy. Electronic address: giulianacangemi@ospedale-gaslini.ge.it.
Giuliana
G
Cangemi
D000293:Adolescent; D014408:Biomarkers, Tumor / Q000652:urine*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D005260:Female; D006719:Homovanillic Acid / Q000652:urine*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007558:Italy; D008297:Male; D009447:Neuroblastoma / Q000175:diagnosis* / Q000652:urine; D012372:ROC Curve; D012016:Reference Values; D014642:Vanilmandelic Acid / Q000652:urine*; D055815:Young Adult
D014408:Biomarkers, Tumor; D014642:Vanilmandelic Acid; D006719:Homovanillic Acid
Homovanillic acid; Neuroblastoma; ROC curve; Reference values; Vanillylmandelic acid