Evaluation of Norepinephrine Transporter Expression and Metaiodobenzylguanidine Avidity in Neuroblastoma: A Report from the Children's Oncology Group

Steven G Dubois, Ethan Geier, Vandana Batra, Sook Wah Yee, John Neuhaus, Mark Segal, Daniel Martinez, Bruce Pawel, Greg Yanik, Arlene Naranjo, Wendy B London, Susan Kreissman, David Baker, Edward Attiyeh, Michael D Hogarty, John M Maris, Kathleen Giacomini, Katherine K Matthay, Steven G Dubois, Ethan Geier, Vandana Batra, Sook Wah Yee, John Neuhaus, Mark Segal, Daniel Martinez, Bruce Pawel, Greg Yanik, Arlene Naranjo, Wendy B London, Susan Kreissman, David Baker, Edward Attiyeh, Michael D Hogarty, John M Maris, Kathleen Giacomini, Katherine K Matthay

Abstract

Purpose. (123)I-metaiodobenzylguanidine (MIBG) is used for the diagnostic evaluation of neuroblastoma. We evaluated the relationship between norepinephrine transporter (NET) expression and clinical MIBG uptake. Methods. Quantitative reverse transcription PCR (N = 82) and immunohistochemistry (IHC; N = 61) were performed for neuroblastoma NET mRNA and protein expression and correlated with MIBG avidity on diagnostic scans. The correlation of NET expression with clinical features was also performed. Results. Median NET mRNA expression level for the 19 MIBG avid patients was 12.9% (range 1.6-73.7%) versus 5.9% (range 0.6-110.0%) for the 8 nonavid patients (P = 0.31). Median percent NET protein expression was 50% (range 0-100%) in MIBG avid patients compared to 10% (range 0-80%) in nonavid patients (P = 0.027). MYCN amplified tumors had lower NET protein expression compared to nonamplified tumors (10% versus 50%; P = 0.0002). Conclusions. NET protein expression in neuroblastoma correlates with MIBG avidity. MYCN amplified tumors have lower NET protein expression.

Figures

Figure 1
Figure 1
Box plot of tumor NET mRNA expression according to tumor avidity for MIBG at initial diagnosis in 27 patients with neuroblastoma (n = 19 with MIBG avid tumors and n = 8 with MIBG nonavid tumors). End of whiskers represent 5th and 95th percentiles. Transporter expression is expressed as a percent of PGK1 expression.
Figure 2
Figure 2
Box plots of percent of tumor cells positive for NET protein (a) and composite NET protein expression score (b) according to tumor avidity for MIBG at initial diagnosis in 23 patients with neuroblastoma (n = 15 with MIBG avid tumors and n = 8 with MIBG nonavid tumors). End of whiskers represent 5th and 95th percentiles.

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