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

Publication ,  Journal Article
Temple, W; Mendelsohn, L; Kim, GE; Nekritz, E; Gustafson, WC; Lin, L; Giacomini, K; Naranjo, A; Van Ryn, C; Yanik, GA; Kreissman, SG ...
Published in: Eur J Nucl Med Mol Imaging
March 2016

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.

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Published In

Eur J Nucl Med Mol Imaging

DOI

EISSN

1619-7089

Publication Date

March 2016

Volume

43

Issue

3

Start / End Page

474 / 481

Location

Germany

Related Subject Headings

  • Vesicular Monoamine Transport Proteins
  • Treatment Outcome
  • Retrospective Studies
  • Nuclear Medicine & Medical Imaging
  • Norepinephrine Plasma Membrane Transport Proteins
  • Neuroblastoma
  • Neoplasm Metastasis
  • Infant
  • Immunohistochemistry
  • Humans
 

Citation

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Temple, W., Mendelsohn, L., Kim, G. E., Nekritz, E., Gustafson, W. C., Lin, L., … DuBois, S. G. (2016). Vesicular monoamine transporter protein expression correlates with clinical features, tumor biology, and MIBG avidity in neuroblastoma: a report from the Children's Oncology Group. Eur J Nucl Med Mol Imaging, 43(3), 474–481. https://doi.org/10.1007/s00259-015-3179-2
Temple, William, Lori Mendelsohn, Grace E. Kim, Erin Nekritz, W Clay Gustafson, Lawrence Lin, Kathy Giacomini, et al. “Vesicular monoamine transporter protein expression correlates with clinical features, tumor biology, and MIBG avidity in neuroblastoma: a report from the Children's Oncology Group.Eur J Nucl Med Mol Imaging 43, no. 3 (March 2016): 474–81. https://doi.org/10.1007/s00259-015-3179-2.
Temple W, Mendelsohn L, Kim GE, Nekritz E, Gustafson WC, Lin L, et al. Vesicular monoamine transporter protein expression correlates with clinical features, tumor biology, and MIBG avidity in neuroblastoma: a report from the Children's Oncology Group. Eur J Nucl Med Mol Imaging. 2016 Mar;43(3):474–81.
Temple, William, et al. “Vesicular monoamine transporter protein expression correlates with clinical features, tumor biology, and MIBG avidity in neuroblastoma: a report from the Children's Oncology Group.Eur J Nucl Med Mol Imaging, vol. 43, no. 3, Mar. 2016, pp. 474–81. Pubmed, doi:10.1007/s00259-015-3179-2.
Temple W, Mendelsohn L, Kim GE, Nekritz E, Gustafson WC, Lin L, Giacomini K, Naranjo A, Van Ryn C, Yanik GA, Kreissman SG, Hogarty M, Matthay KK, DuBois SG. Vesicular monoamine transporter protein expression correlates with clinical features, tumor biology, and MIBG avidity in neuroblastoma: a report from the Children's Oncology Group. Eur J Nucl Med Mol Imaging. 2016 Mar;43(3):474–481.
Journal cover image

Published In

Eur J Nucl Med Mol Imaging

DOI

EISSN

1619-7089

Publication Date

March 2016

Volume

43

Issue

3

Start / End Page

474 / 481

Location

Germany

Related Subject Headings

  • Vesicular Monoamine Transport Proteins
  • Treatment Outcome
  • Retrospective Studies
  • Nuclear Medicine & Medical Imaging
  • Norepinephrine Plasma Membrane Transport Proteins
  • Neuroblastoma
  • Neoplasm Metastasis
  • Infant
  • Immunohistochemistry
  • Humans