Detection of tyrosine hydroxylase m-RNA in the peripheral blood of neuroblastoma patients and its relation to treatment response

Abstract

Background Neuroblastoma (NB) is the most common malignant solid tumor in childhood and, among all childhood malignancies, is second only to leukemia. NB originates before birth in the neural crest. Tyrosine hydroxylase (TH) is the first enzyme in the pathway of catecholamine synthesis and the detection of TH m-RNA is very useful as a tumor marker for NB. Aim of the study The aim of the present study is to detect the TH m-RNA in the peripheral blood of patients with NB by real-time reverse transcriptase-PCR (RT-PCR) at diagnosis and during therapy to determine the role of TH m-RNA in the diagnosis of NB and its relation to the treatment response. Patients and methods Blood samples were collected from 32 children with advanced stages NB (stages III and IV), either newly diagnosed (n=11) or receiving treatment (n=21). Another 12 blood samples were also obtained from age-matched children with other pediatric cancers as a control group. We used real-time RT-PCR for the detection of TH m-RNA. Results TH m-RNA expression was detected in peripheral blood samples obtained from five of 11 (45.4%) newly diagnosed cases and in five of 19 (26.3%) children receiving treatment. A significant difference was found between stages (III and VI) at presentation (P=0.04), LDH level (P=0.04), and bone marrow disease (P=0.025) with the detection of TH m-RNA in peripheral blood. Although no significant effect on survival outcomes had been reported in our patients, there were significant differences (P=0.04) in the response to treatment and TH m-RNA expression. Conclusion Detection of TH m-RNA by real-time RT-PCR is a reliable, quick, and easy way to detect the expression of NB cell in blood at diagnosis. Also, TH expression can be used as a tumor marker for the accurate diagnosis of NB and a predictor of treatment response.