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Eur J Nucl Med Mol Imaging. 2016 Mar;43(3):474-481. doi: 10.1007/s00259-015-3179-2. Epub 2015 Sep 4.

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

Author information

1
Department of Pediatrics, UCSF School of Medicine, San Francisco, CA 94143.
2
UCSF Benioff Children's Hospital, San Francisco, CA 94158.
3
Department of Pathology, UCSF School of Medicine, San Francisco, CA 94143.
4
Department of Bioengineering and Therapeutic Sciences, UCSF School of Pharmacy, San Francisco, CA 94143.
5
Children's Oncology Group Statistics and Data Center, University of Florida, Gainesville, FL 32607.
6
CS Mott Children's Hospital, University of Michigan, Ann Arbor, MI 48109.
7
Duke University Medical Center, Durham, NC 27710.
8
Children's Hospital of Philadelphia and Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104.
#
Contributed equally

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 (nā€‰=ā€‰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; pā€‰=ā€‰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.

KEYWORDS:

MIBG avidity; Neuroblastoma; VMAT1; VMAT2; Vesicular monoamine transporters

PMID:
26338179
PMCID:
PMC4733400
[Available on 2017-03-01]
DOI:
10.1007/s00259-015-3179-2
[Indexed for MEDLINE]
Free PMC Article

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