Neuroblastoma is frequent childhood malignant tumor with high clinical heterogeneity. Despite the rare mutations of TP53 gene, p53-mediated pathway is often inactivated in neuroblastoma. The significance of MDM2, p53 direct antagonist, overexpression in neuroblastoma clinical course and outcome has been already established. But still remain patients with favorable clinical features and poor disease outcome.
The case group comprised 68 children with neuroblastoma (mean age: 36.7±4.7 months; primary tumors: 88%; MYCN+: 39%; MDM2 overexpressed: 70%). p53 mRNA expression level (EL) was analyzed in tumor samples with qRT-PCR and evaluated by the ΔΔCt method according to control GAPDH mRNA EL.
We established that the value of p53 EL in neuroblastoma cells varied in wide limits. Significantly lower p53 EL was detected in recurrent and metastatic tumor samples comparing to primary tumors (P = 0.001). Insignificant increase of p53 EL in patients with unfavorable clinical and biological features (late occurrence age, IV stage, MYCN amplification) was observed. However, we revealed significant increase of p53 EL in MDM2 overexpressed tumors (P = 0.007). With ROC-analysis we assessed the optimal criterions for distribution of patients according to p53 expression (OC:>1.18 a.u., P = 0.04, AUC:0.69 for high and OC:
Regulation of p53-mediated pathway is complex and multicomponent system. Alteration of p53 EL is independent from clinical features marker of neuroblastoma. Analysis of p53/MDM2 co-expression provides the possibility for better neuroblastoma outcome prediction.
Clinical trial identification
Legal entity responsible for the study
National Cancer Institute of Ministry of Public Health of Ukraine
All authors have declared no conflicts of interest.