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 Cheung, I. Y. Articles by Cheung, N.-K. V. Search for Related Content PubMed PubMed Citation Articles by Cheung, I. Y. Articles by Cheung, N.-K. V. Social Bookmarking                            What's this?

Quantitation of GD2 Synthase mRNA by Real-Time Reverse Transcriptase Polymerase Chain Reaction: Clinical Utility in Evaluating Adjuvant Therapy in Neuroblastoma

Irene Y. Cheung, M. Serena Lo Piccolo, Brian H. Kushner, Kim Kramer, Nai-Kong V. Cheung

From the Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, New York, NY.

Address reprint requests to Irene Y. Cheung, ScD, Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, New York, NY 10021; email: cheungi{at}mskcc.org.

Purpose: Minimal residual disease (MRD) is one of the final hurdles to cancer cure. Because therapy (myeloablation, immunotherapy, or differentiation) for MRD is applied at the time of clinical remission, objective surrogate markers are needed to gauge treatment efficacy.

Patients and Methods: Using quantitative reverse transcriptase polymerase chain reaction (RT-PCR) of GD2 synthase (ß1,4-N-acetylgalactosaminyltransferase, EC 2.4.1.92) mRNA, we evaluated MRD response to anti-GD2 monoclonal antibody 3F8 adjuvant therapy, namely, one cycle of radioimmunotherapy using iodine-131 (¹³¹I)-3F8 plus one cycle of unlabeled 3F8 in 45 stage 4 neuroblastoma patients (newly diagnosed or without prior relapse) on the N7 protocol at Memorial Sloan-Kettering Cancer Center. The prognostic effect of MRD in their bone marrows before and after this phase of adjuvant therapy on progression-free survival (PFS) and overall survival (OS) was also analyzed.

Results: Before 3F8 treatment, 24 of 45 patients were in complete remission (CR), 12 were in very good partial remission (VGPR), and nine were in partial remission (PR), according to criteria from International Neuroblastoma Staging System plus ¹³¹I-3F8 scan; 71% had detectable tumor cells in marrow by real-time RT-PCR. Of the 32 positive patients, 20 became negative after therapy, with a 63% efficacy. When patients were stratified by CR/VGPR versus PR, GD2 synthase positivity was prognostic when detected before 3F8-targeted therapy (PFS, P = .045 and OS, P = .010). Persistent marker positivity was also predictive of PFS (P = .035) and OS (P = .027). Patients who succumbed to the disease had transcript levels four times higher than those who remain alive.

Conclusion: GD2 synthase mRNA is a useful surrogate marker for evaluating adjuvant treatment efficacy in neuroblastoma with prognostic potential.

Supported in part by grants from the National Institutes of Health (CA61017 and CA095742) and the Robert Steel Foundation, Hope Street Kids, Pediatric Cancer Foundation, and Katie’s Find A Cure Fund.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				J. Stutterheim, A. Gerritsen, L. Zappeij-Kannegieter, B. Yalcin, R. Dee, M. M. van Noesel, F. Berthold, R. Versteeg, H. N. Caron, C. E. van der Schoot, et al. Detecting Minimal Residual Disease in Neuroblastoma: The Superiority of a Panel of Real-Time Quantitative PCR Markers Clin. Chem., July 1, 2009; 55(7): 1316 - 1326. [Abstract] [Full Text] [PDF]

				I. Y. Cheung, Y. Feng, W. Gerald, and N.-K. V. Cheung Exploiting Gene Expression Profiling to Identify Novel Minimal Residual Disease Markers of Neuroblastoma Clin. Cancer Res., November 1, 2008; 14(21): 7020 - 7027. [Abstract] [Full Text] [PDF]

				I. Y. Cheung, Y. Feng, A. Vickers, W. Gerald, and N.-K. V. Cheung Cyclin D1, a Novel Molecular Marker of Minimal Residual Disease, in Metastatic Neuroblastoma J. Mol. Diagn., April 1, 2007; 9(2): 237 - 241. [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]

				M. V. Corrias, R. Haupt, B. Carlini, S. Parodi, L. Rivabella, A. Garaventa, V. Pistoia, and S. Dallorso Peripheral blood stem cell tumor cell contamination and survival of neuroblastoma patients. Clin. Cancer Res., October 1, 2006; 12(19): 5680 - 5685. [Abstract] [Full Text] [PDF]

				N.-K. V. Cheung, R. Sowers, A. J. Vickers, I. Y. Cheung, B. H. Kushner, and R. Gorlick FCGR2A Polymorphism Is Correlated With Clinical Outcome After Immunotherapy of Neuroblastoma With Anti-GD2 Antibody and Granulocyte Macrophage Colony-Stimulating Factor J. Clin. Oncol., June 20, 2006; 24(18): 2885 - 2890. [Abstract] [Full Text] [PDF]

				K. Swerts, B. De Moerloose, C. Dhooge, J. Vandesompele, C. Hoyoux, K. Beiske, Y. Benoit, G. Laureys, and J. Philippe Potential Application of ELAVL4 Real-Time Quantitative Reverse Transcription-PCR for Detection of Disseminated Neuroblastoma Cells Clin. Chem., March 1, 2006; 52(3): 438 - 445. [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]

				I. Y. Cheung, M. S. Lo Piccolo, B. H. Kushner, and N.-K. V. Cheung Early Molecular Response of Marrow Disease to Biologic Therapy Is Highly Prognostic in Neuroblastoma J. Clin. Oncol., October 15, 2003; 21(20): 3853 - 3858. [Abstract] [Full Text] [PDF]