Detecting Minimal Residual Disease in Neuroblastoma: Still a Ways to Go

Neuroblastoma is the most common extracranial solid tumor of childhood and accounts for 10% of all cancers in children. The development of neuroblastoma involves both embryonic and tumorigenic factors, making the tumor very heterogeneous both biologically and clinically. Neuroblastoma tumors originate from embryonic neural crest cells committed to the development of the sympathetic nervous system, and their malignancy varies from totally benign with spontaneous regression to highly malignant (1). Prognostic factors include age of the patient at diagnosis, INSS (International Neuroblastoma Staging System) stage, tumor histopathology, and ploidy status of DNA content (2). Despite the availability of many clinical and biologic markers proposed as predictive of disease outcome and the use of advanced multimodal therapy, treatment results are still suboptimal for patients with these tumors. Thus, how to best estimate patient prognosis and choose optimal individual therapy remain fundamental challenges.Since the discovery by Moss et al. (3) 20 years ago of neuroblastoma cells in the blood of a majority of patients with known disseminated disease, much work has been devoted to the development and improvement of methods for detection of minimal residual disease (MRD).1In this issue of Clinical Chemistry Stutterheim et al. (4) address the question of how to best identify the presence of neuroblastoma cells in blood and bone marrow by use of reverse transcription quantitative PCR (RQ-PCR). The authors recently investigated the use of paired-like homeobox 2b ( PHOX2B )2 as a marker for MRD in neuroblastoma and claimed reported that this transcript was the most specific single marker for this purpose (5). In the current study they selected 28 genes from SAGE libraries that showed high expression in neuroblastoma tumors and little or no expression in normal tissues. Preliminary studies of these 28 genes and 5 previously described markers (identified by using RQ-PCR and …