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

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

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)474-481
Number of pages8
JournalEuropean Journal of Nuclear Medicine and Molecular Imaging
Volume43
Issue number3
DOIs
StatePublished - Mar 1 2016

Bibliographical note

Funding Information:
This work was supported by the Campini Foundation (S.G.D. and K.K.M.), the Dougherty Family Foundation (K.K.M.), Alex’s Lemonade Stand Foundation (W.T., S.G.D., and K.K.M.), U10CA09853, U10CA180899, and U24CA114766. The funding sources did not play a role in study design, conduct, data analysis, or interpretation. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the principles of the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards. For this type of study, formal consent is not required. William Temple and Lori Mendelsohn contributed equally to this work.

Keywords

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

Fingerprint Dive into the research topics of 'Vesicular monoamine transporter protein expression correlates with clinical features, tumor biology, and MIBG avidity in neuroblastoma: a report from the Children’s Oncology Group'. Together they form a unique fingerprint.

Cite this