Universität zu Köln

Peitzsch, Mirko, Butch, Elizabeth R., Lovorn, Elizabeth, Mangelis, Anastasios, Furman, Wayne L., Santana, Victor M., Hero, Barbara, Berthold, Frank ORCID: 0000-0002-7613-1723, Shulkin, Barry L., Huebner, Angela and Eisenhofer, Graeme . Biochemical testing for neuroblastoma using plasma free 3-O-methyldopa, 3-methoxytyramine, and normetanephrine. Pediatr. Blood Cancer. HOBOKEN: WILEY. ISSN 1545-5017

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Abstract

Background Neuroblastoma, the most common extracranial solid tumor of childhood, produces catecholamines that are metabolized within tumor cells. Homovanillic acid (HVA) and vanillylmandelic acid (VMA), the end products of catecholamine metabolism, have limited accuracy for testing of the tumors. This study assessed whether metabolites produced in earlier steps of catecholamine metabolism might offer improved diagnostic accuracy over urinary HVA and VMA. Procedure Plasma concentrations of 3-methoxytyramine, normetanephrine, and metanephrine were measured in two pediatric cohorts: (i) 96 children with confirmed neuroblastoma and (ii) 41 children with signs and symptoms of a catecholamine-producing tumor or other neoplasms and in whom neuroblastoma was excluded. Additional measurements of plasma 3-O-methyldopa and relationships of metabolites to MYCN amplification were examined in patient subgroups. Results Overall, 94 of the 96 patients with neuroblastoma had concentrations of 3-methoxytyramine or normetanephrine above age-specific upper limits of reference intervals, providing a diagnostic sensitivity of 97.9% that was higher (P < 0.0001) than that of 82.2% for HVA and VMA. One of the two patients with normal plasma results showed an elevation of plasma 3-O-methyldopa. Diagnostic specificities were, respectively, 95.1% and 84.8%. Areas under receiver-operating characteristic curves confirmed the superior diagnostic power of the plasma than the urinary test (0.994 vs 0.945; P = 0.0095). Ratios of plasma 3-methoxytyramine to normetanephrine were 7.2-fold higher (P < 0.0001) for patients who had neuroblastomas with MYCN amplification than without MYCN amplification. Conclusions Measurements of plasma 3-methoxytyramine and normetanephrine provide a highly accurate diagnostic test for neuroblastoma and also offer potential for prognostic risk stratification.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Peitzsch, Mirko UNSPECIFIED UNSPECIFIED UNSPECIFIED Butch, Elizabeth R. UNSPECIFIED UNSPECIFIED UNSPECIFIED Lovorn, Elizabeth UNSPECIFIED UNSPECIFIED UNSPECIFIED Mangelis, Anastasios UNSPECIFIED UNSPECIFIED UNSPECIFIED Furman, Wayne L. UNSPECIFIED UNSPECIFIED UNSPECIFIED Santana, Victor M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Hero, Barbara UNSPECIFIED UNSPECIFIED UNSPECIFIED Berthold, Frank UNSPECIFIED orcid.org/0000-0002-7613-1723 UNSPECIFIED Shulkin, Barry L. UNSPECIFIED UNSPECIFIED UNSPECIFIED Huebner, Angela UNSPECIFIED UNSPECIFIED UNSPECIFIED Eisenhofer, Graeme UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-127672
DOI:	10.1002/pbc.28081
Journal or Publication Title:	Pediatr. Blood Cancer
Publisher:	WILEY
Place of Publication:	HOBOKEN
ISSN:	1545-5017
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language CATECHOL-O-METHYLTRANSFERASE; URINARY CATECHOLAMINES; VANILLYLMANDELIC ACID; LIQUID-CHROMATOGRAPHY; REFERENCE INTERVALS; DIAGNOSIS; METABOLITES; METANEPHRINES; DOPAMINE; MARKERS Multiple languages Oncology; Hematology; Pediatrics Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/12767