BACKGROUND: The presence of bone marrow (BM) metastasis and circulating tumor cells in patients with neuroblastoma is a significant prognostic factor at diagnosis and might antedate detection of a relapse by other diagnostic studies. In this study, the clinical value of reverse transcription-polymerase chain reaction (RT-PCR) to amplify mRNA for tyrosine hydroxylase (TH) and magnetic resonance imaging (MRI) during the clinical course of patients with advanced neuroblastoma, was evaluated. METHODS: Four patients with Stage 1, 4 or 4S neuroblastoma, were studied. BM and peripheral blood (PB), including peripheral blood stem cell (PBSC), samples were examined for TH mRNA using RT-PCR. Concurrently, MRI detection of BM metastasis was used. RESULTS: In all cases, except one that had no evidence of BM invasion, TH mRNA in BM and PB at diagnosis were positive, and TH mRNA at diagnosis disappeared after chemotherapy. In two cases, although involvement in the neurocentrum BM was detected by MRI, TH mRNA in the iliac crest BM was negative. The pathological area still remained on MRI after intensive therapy. CONCLUSION: RT-PCR for TH mRNA might be the most sensitive method for the detection of occult neuroblastoma cells in BM and PB. However, because invasion of the BM by neuroblastoma may have a focal distribution, sampling errors can occur. Therefore, not only RT-PCR but also MRI, need to be used to rule out marrow involvement, especially at diagnosis and BM relapse.
BACKGROUND: The presence of bone marrow (BM) metastasis and circulating tumor cells in patients with neuroblastoma is a significant prognostic factor at diagnosis and might antedate detection of a relapse by other diagnostic studies. In this study, the clinical value of reverse transcription-polymerase chain reaction (RT-PCR) to amplify mRNA for tyrosine hydroxylase (TH) and magnetic resonance imaging (MRI) during the clinical course of patients with advanced neuroblastoma, was evaluated. METHODS: Four patients with Stage 1, 4 or 4S neuroblastoma, were studied. BM and peripheral blood (PB), including peripheral blood stem cell (PBSC), samples were examined for TH mRNA using RT-PCR. Concurrently, MRI detection of BM metastasis was used. RESULTS: In all cases, except one that had no evidence of BM invasion, TH mRNA in BM and PB at diagnosis were positive, and TH mRNA at diagnosis disappeared after chemotherapy. In two cases, although involvement in the neurocentrum BM was detected by MRI, TH mRNA in the iliac crest BM was negative. The pathological area still remained on MRI after intensive therapy. CONCLUSION: RT-PCR for TH mRNA might be the most sensitive method for the detection of occult neuroblastoma cells in BM and PB. However, because invasion of the BM by neuroblastoma may have a focal distribution, sampling errors can occur. Therefore, not only RT-PCR but also MRI, need to be used to rule out marrow involvement, especially at diagnosis and BM relapse.