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European Journal of Nuclear Medicine and Molecular Imaging
Published in: European Journal of Nuclear Medicine and Molecular Imaging 3/2016

01-03-2016 | Original Article

Vesicular monoamine transporter protein expression correlates with clinical features, tumor biology, and MIBG avidity in neuroblastoma: a report from the Children’s Oncology Group

Authors: William Temple, Lori Mendelsohn, Grace E. Kim, Erin Nekritz, W. Clay Gustafson, Lawrence Lin, Kathy Giacomini, Arlene Naranjo, Collin Van Ryn, Gregory A. Yanik, Susan G. Kreissman, Michael Hogarty, Katherine K. Matthay, Steven G. DuBois

Published in: European Journal of Nuclear Medicine and Molecular Imaging | Issue 3/2016

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Abstract

Purpose

Vesicular monoamine transporters 1 and 2 (VMAT1 and VMAT2) are thought to mediate MIBG uptake in adult neuroendocrine tumors. In neuroblastoma, the norepinephrine transporter (NET) has been investigated as the principal MIBG uptake protein, though some tumors without NET expression concentrate MIBG. We investigated VMAT expression in neuroblastoma and correlated expression with MIBG uptake and clinical features.

Methods

We evaluated VMAT1 and VMAT2 expression by immunohistochemistry (IHC) in neuroblastoma tumors from 76 patients with high-risk metastatic disease treated in a uniform cooperative group trial (COG A3973). All patients had baseline MIBG diagnostic scans centrally reviewed. IHC results were scored as the product of intensity grading (0 – 3+) and percent of tumor cells expressing the protein of interest. The association between VMAT1 and VMAT2 scores and clinical and biological features was tested using Wilcoxon rank-sum tests.

Results

Patient characteristics were typical of high-risk neuroblastoma, though the cohort was intentionally enriched in patients with MIBG-nonavid tumors (n = 20). VMAT1 and VMAT2 were expressed in 62 % and 75 % of neuroblastoma tumors, respectively. VMAT1 and VMAT2 scores were both significantly lower in MYCN amplified tumors and in tumors with high mitotic karyorrhectic index. MIBG-avid tumors had significantly higher VMAT2 scores than MIBG-nonavid tumors (median 216 vs. 45; p = 0.04). VMAT1 expression did not correlate with MIBG avidity.

Conclusion

VMAT1 and VMAT2 are expressed in the majority of neuroblastomas. Expression correlates with other biological features. The expression level of VMAT2 but not that of VMAT1 correlates with avidity for MIBG.
Appendix
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Metadata
Title
Vesicular monoamine transporter protein expression correlates with clinical features, tumor biology, and MIBG avidity in neuroblastoma: a report from the Children’s Oncology Group
Authors
William Temple
Lori Mendelsohn
Grace E. Kim
Erin Nekritz
W. Clay Gustafson
Lawrence Lin
Kathy Giacomini
Arlene Naranjo
Collin Van Ryn
Gregory A. Yanik
Susan G. Kreissman
Michael Hogarty
Katherine K. Matthay
Steven G. DuBois
Publication date
01-03-2016
Publisher
Springer Berlin Heidelberg
Published in
European Journal of Nuclear Medicine and Molecular Imaging / Issue 3/2016
Print ISSN: 1619-7070
Electronic ISSN: 1619-7089
DOI
https://doi.org/10.1007/s00259-015-3179-2

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