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

Author:

DuBois Steven G.1,Geier Ethan2,Batra Vandana3,Yee Sook Wah2,Neuhaus John4,Segal Mark4,Martinez Daniel5,Pawel Bruce5,Yanik Greg6,Naranjo Arlene78,London Wendy B.89,Kreissman Susan10,Baker David11,Attiyeh Edward3,Hogarty Michael D.3,Maris John M.3,Giacomini Kathleen2,Matthay Katherine K.1

Affiliation:

1. Department of Pediatrics, UCSF School of Medicine, 505 Parnassus Avenue, M696, San Francisco, CA 94143-0106, USA

2. Department of Bioengineering and Therapeutic Sciences, UCSF Schools of Pharmacy and Medicine, San Francisco, CA 94143-0912, USA

3. Department of Pediatrics, Children’s Hospital of Philadelphia, University of Pennsylvania, Philadelphia, PA 19104, USA

4. Epidemiology and Biostatistics, UCSF School of Medicine, San Francisco, CA 94107, USA

5. Department of Pathology, Perelman School of Medicine, Children’s Hospital of Philadelphia, University of Pennsylvania, Philadelphia, PA 19104, USA

6. Department of Pediatrics, University of Michigan Medical School, Ann Arbor, MI 48109, USA

7. Department of Biostatistics, University of Florida, Gainesville, FL 32611, USA

8. Children's Oncology Group Statistics and Data Center, Arcadia, CA 91006-3776, USA

9. Department of Pediatrics, Children's Hospital Boston and Dana-Farber Harvard Cancer Center, Boston, MA 02215-5450, USA

10. Department of Pediatrics, Duke University School of Medicine, Durham, NC 27705, USA

11. Department of Hematology/Oncology, Princess Margaret Hospital for Children, Perth, WA 6008, Australia

Abstract

Purpose. 123I-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.

Funder

Campini Foundation

Publisher

Hindawi Limited

Subject

Radiology Nuclear Medicine and imaging

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