Useful markers for detecting minimal residual disease in cases of neuroblastoma

Neuroblastoma (NB), which is a malignant tumor of young children derived from neural crest cells that occurs in children, exhibits a wide range of clinical behaviors, from spontaneous regression to rapid progression. Advanced NB patients have a poor prognosis, and recently, autologous bone marrow transplantation (BMT) and autologous peripheral blood stem cell transplantation (PBSCT) have been attempted to improve the prognosis of these patients. In this study, we attempted to detect the expression of tyrosine hydroxylase (TH), neuroendocrine protein gene product (PGP) 9.5, ELAVL-4 and GD2 synthetase (GALGT), all of which are highly expressed in NBs, by the reverse transcription-polymerase chain reaction (RT-PCR) technique in order to detect minimal residual disease (MRD) in the bone marrow (BM) and peripheral blood (PB). Analysis of various tumor cell lines (Ewing's sarcoma, hepatoma, leukemias, and breast cancer cell lines in addition to NBs), and human normal samples (BM and PB cells) revealed that TH was the most specific marker for the detection of NB. On the other hand, PGP9.5 was the most sensitive marker, and was detected even when there was only one positive cell per 10(7) negative cells. We concluded that TH is a better marker before the diagnosis of NB while PGP9.5 is a better marker to detect MRD after the diagnosis. Here, we describe our results on useful markers to detect MRD in patients with NB.