Expression of Wilms tumor gene in high risk neuroblastoma: complementary marker to tyrosine hydroxylase for detection of minimal residual disease.

BACKGROUND

Neuroblastoma (NB) is an enigmatic tumor that often presents with metastatic disease at diagnosis and it is this aggressive propensity which places it among the deadliest pediatric tumors despite intensive multimodal therapy including hematopoietic stem cell transplantation (HSCT). We have previously demonstrated that Wilms tumor 1 gene (WT1) is a surrogate marker of proliferation in leukemia. To determine the potential association between WT1 and a known marker of NB, tyrosine hydroxylase (TH) in this high risk group of patients.

METHODS

A total of 141 random samples from 34 patients were obtained, at diagnosis (n=27), during therapy (n=95), in clinical remission (n=13), and at the time of relapse (n=6). Quantitative RT-PCR was used for the evaluation of the level of gene expression using specific primers.

RESULTS

Although similar gene expressions were demonstrated in both controls when evaluating both genes, significant difference was found at each clinical time point. Furthermore, when comparing patient samples from diagnosis to clinical remission and diagnosis to clinical relapse, individual gene expression varied. WT1 demonstrated significance (P=0.0002) and insignificance (P=0.06) whereas TH remained non-significant (P=0.2, P=0.09) respectively.

CONCLUSIONS

WT1 gene is indicative of cellular proliferation in NB and for this reason it can be adjuvant to TH for the detection minimal residual disease (MRD).