Molecular detection of tyrosine hydroxylase in the peripheral blood of patients with neuroblastoma: Useful at diagnosis but not predictive of subsequent relapse during off-therapy follow-up

In the present study, the authors analyzed the tyrosine hydroxylase (TH) expression in peripheral blood (PB) of neuroblastoma (NB) patients and investigated the clinical implications. From April 2005 to October 2008, a total of 683 PB specimens (64 at diagnosis, 244 during chemotherapy, 355 during off-therapy follow-up, and 20 at relapse) acquired from 141 patients were investigated. TH expression was measured by quantitative reverse transcriptase-polymerase chain reaction (RT-PCR). TH-positive rate at diagnosis (21.4%) was higher than those during chemotherapy (0.8%) or off-therapy follow-up (1.7%). TH expression at diagnosis was associated with high-risk features (ie, advanced stage, older age, unfavorable pathology, and amplified N-myc) and the probability of 3-year relapse-free survival in the TH-positive patients was lower than in the TH-negative patients (45.8% ± 27.8% versus 95.8% ± 5.7%, P < .001). TH expression was positive in only 6 specimens during off-therapy follow-up. However, tumor relapse occurred in only 2 out of 6 TH-positive patients. In addition, TH expression was negative during previous off-therapy follow-up, prior to relapse, in 8 out of 10 relapsed patients. Whereas TH expression in PB at diagnosis was associated with high-risk features and a poorer outcome, TH expression during off-therapy follow-up had very limited value for the prediction of a subsequent relapse.