This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Cohn, S. L. Articles by Haber, M. Search for Related Content PubMed PubMed Citation Articles by Cohn, S. L. Articles by Haber, M.

MYCN Expression Is Not Prognostic of Adverse Outcome in Advanced-Stage Neuroblastoma With Nonamplified MYCN

From the Department of Pediatrics, Northwestern University Medical School; Children’s Memorial Hospital and Robert H. Lurie Comprehensive Cancer Center, Chicago, IL; Department of Statistics, University of Florida, and Pediatric Oncology Group Statistical Office, Gainesville, FL; and Children’s Cancer Institute Australia for Medical Research, University of New South Wales, and Sydney Children’s Hospital, Sydney, Australia.

Address reprint requests to Susan L. Cohn, MD, Division of Hematology/Oncology, Box 30, Children’s Memorial Hospital, 2300 Children’s Plaza, Chicago, IL 60614; email scohn{at}northwestern.edu

PURPOSE: The clinical significance of MYCN expression in children with neuroblastoma (NB) remains controversial. To determine the prognostic significance of MYCN expression in the absence of MYCN amplification, we analyzed MYCN mRNA and protein expression in tumors from 69 patients.

PATIENTS AND METHODS: Sixty-nine NB tumor samples with nonamplified MYCN from patients with stage C or D disease were obtained from the Pediatric Oncology Group Neuroblastoma Tumor Bank. MYCN mRNA was analyzed using a real-time reverse transcriptase polymerase chain reaction assay, and MYCN protein was examined by Western blot analyses.

RESULTS: The estimated 5-year event-free survival (EFS) and survival (S) rates plus SE for the cohort were 57% ± 17% and 60% ± 16%, respectively. Infants younger than 1 year had significantly higher rates of EFS and S than children 1 year of age (P = .003 and P < .001, respectively); patients with stage C disease had better outcome than those with stage D NB (P < .001); and patients with hyperdiploid tumors had better outcome than those with diploid NB (P < .001). Surprisingly, outcome was slightly better for patients with high versus low levels of MYCN mRNA expression (4-year S, 70% ± 13% v 50% ± 16%; P = .290), and for patients with tumors that expressed MYCN protein (4-year S, 73% ± 19% v 53% ± 15%, respectively; P = .171).

CONCLUSION: High levels of MYCN expression are not prognostic of adverse outcome in patients with advanced-stage NB with nonamplified MYCN. A trend associating high levels of MYCN expression with improved outcome was observed.

This article has been cited by other articles:

				E. Fredlund, M. Ringner, J. M. Maris, and S. Pahlman High Myc pathway activity and low stage of neuronal differentiation associate with poor outcome in neuroblastoma PNAS, September 16, 2008; 105(37): 14094 - 14099. [Abstract] [Full Text] [PDF]

				C. Stock, E. Bozsaky, F. Watzinger, U. Poetschger, L. Orel, T. Lion, A. Kowalska, and P. F. Ambros Genes Proximal and Distal to MYCN Are Highly Expressed in Human Neuroblastoma as Visualized by Comparative Expressed Sequence Hybridization Am. J. Pathol., January 1, 2008; 172(1): 203 - 214. [Abstract] [Full Text] [PDF]

				F. Westermann, K.-O. Henrich, J. S. Wei, W. Lutz, M. Fischer, R. Konig, R. Wiedemeyer, V. Ehemann, B. Brors, K. Ernestus, et al. High Skp2 Expression Characterizes High-Risk Neuroblastomas Independent of MYCN Status Clin. Cancer Res., August 15, 2007; 13(16): 4695 - 4703. [Abstract] [Full Text] [PDF]

				A. Schramm, J. Vandesompele, J. H. Schulte, S. Dreesmann, L. Kaderali, B. Brors, R. Eils, F. Speleman, and A. Eggert Translating Expression Profiling into a Clinically Feasible Test to Predict Neuroblastoma Outcome Clin. Cancer Res., March 1, 2007; 13(5): 1459 - 1465. [Abstract] [Full Text] [PDF]

				L. Chesler, C. Schlieve, D. D. Goldenberg, A. Kenney, G. Kim, A. McMillan, K. K. Matthay, D. Rowitch, and W. A. Weiss Inhibition of Phosphatidylinositol 3-Kinase Destabilizes Mycn Protein and Blocks Malignant Progression in Neuroblastoma Cancer Res., August 15, 2006; 66(16): 8139 - 8146. [Abstract] [Full Text] [PDF]

				X. X. Tang, H. Zhao, B. Kung, D. Y. Kim, S. L. Hicks, S. L. Cohn, N.-K. Cheung, R. C. Seeger, A. E. Evans, and N. Ikegaki The MYCN Enigma: Significance of MYCN Expression in Neuroblastoma. Cancer Res., March 1, 2006; 66(5): 2826 - 2833. [Abstract] [Full Text] [PDF]

				M. Fischer, M. Skowron, and F. Berthold Reliable Transcript Quantification by Real-Time Reverse Transcriptase-Polymerase Chain Reaction in Primary Neuroblastoma Using Normalization to Averaged Expression Levels of the Control Genes HPRT1 and SDHA J. Mol. Diagn., February 1, 2005; 7(1): 89 - 96. [Abstract] [Full Text] [PDF]

				H. M. Katzenstein, S. L. Cohn, R. M. Shore, D. M.E. Bardo, P. R. Haut, M. Olszewski, J. Schmoldt, D. Liu, A. W. Rademaker, and M. Kletzel Scintigraphic Response by 123I-Metaiodobenzylguanidine Scan Correlates With Event-Free Survival in High-Risk Neuroblastoma J. Clin. Oncol., October 1, 2004; 22(19): 3909 - 3915. [Abstract] [Full Text] [PDF]

				L. M. Hansford, W. D. Thomas, J. M. Keating, C. A. Burkhart, A. E. Peaston, M. D. Norris, M. Haber, P. J. Armati, W. A. Weiss, and G. M. Marshall Mechanisms of embryonal tumor initiation: Distinct roles for MycN expression and MYCN amplification PNAS, August 24, 2004; 101(34): 12664 - 12669. [Abstract] [Full Text] [PDF]

				Q. Yang, S. Liu, Y. Tian, C. Hasan, D. Kersey, H. R. Salwen, A. Chlenski, E. J. Perlman, and S. L. Cohn Methylation-Associated Silencing of the Heat Shock Protein 47 Gene in Human Neuroblastoma Cancer Res., July 1, 2004; 64(13): 4531 - 4538. [Abstract] [Full Text] [PDF]

				A. Weber, C. Huesken, E. Bergmann, W. Kiess, N. M. Christiansen, and H. Christiansen Coexpression of Insulin Receptor-Related Receptor and Insulin-Like Growth Factor 1 Receptor Correlates with Enhanced Apoptosis and Dedifferentiation in Human Neuroblastomas Clin. Cancer Res., November 15, 2003; 9(15): 5683 - 5692. [Abstract] [Full Text] [PDF]

				M. Alaminos, J. Mora, N.-K. V. Cheung, A. Smith, J. Qin, L. Chen, and W. L. Gerald Genome-wide Analysis of Gene Expression Associated with MYCN in Human Neuroblastoma Cancer Res., August 1, 2003; 63(15): 4538 - 4546. [Abstract] [Full Text] [PDF]

				T. Tajiri, X. Liu, P. M. Thompson, S. Tanaka, S. Suita, H. Zhao, J. M. Maris, G. C. Prendergast, and M. D. Hogarty Expression of a MYCN-interacting Isoform of the Tumor Suppressor BIN1 Is Reduced in Neuroblastomas with Unfavorable Biological Features Clin. Cancer Res., August 1, 2003; 9(9): 3345 - 3355. [Abstract] [Full Text] [PDF]

				J. L. Weinstein, H. M. Katzenstein, and S. L. Cohn Advances in the Diagnosis and Treatment of Neuroblastoma Oncologist, June 1, 2003; 8(3): 278 - 292. [Abstract] [Full Text] [PDF]

				L. H. J. Lambooy, C. E. M. Gidding, L. P. van den Heuvel, C. A. Hulsbergen-van de Kaa, M. Ligtenberg, J. P. M. Bokkerink, and R. A. De Abreu Real-Time Analysis of Tyrosine Hydroxylase Gene Expression: A Sensitive and Semiquantitative Marker for Minimal Residual Disease Detection of Neuroblastoma Clin. Cancer Res., February 1, 2003; 9(2): 812 - 819. [Abstract] [Full Text] [PDF]

				A. Lasorella, R. Boldrini, C. Dominici, A. Donfrancesco, Y. Yokota, A. Inserra, and A. Iavarone Id2 Is Critical for Cellular Proliferation and Is the Oncogenic Effector of N-Myc in Human Neuroblastoma Cancer Res., January 1, 2002; 62(1): 301 - 306. [Abstract] [Full Text] [PDF]

				K. K. Matthay MYCN Expression in Neuroblastoma: A Mixed Message? J. Clin. Oncol., November 1, 2000; 18(21): 3591 - 3594. [Full Text] [PDF]

				C. F. Manohar, M. L. Short, A. Nguyen, N. N. Nguyen, D. Chagnovich, Q. Yang, and S. L. Cohn HuD, a Neuronal-specific RNA-binding Protein, Increases the in Vivo Stability of MYCN RNA J. Biol. Chem., January 11, 2002; 277(3): 1967 - 1973. [Abstract] [Full Text] [PDF]