Measurement of Tyrosine Hydroxylase Transcripts in Bone Marrow Using Biopsied Tissue Instead of Aspirates for Neuroblastoma

Background. Molecular detection of tyrosine hydroxylase (TH) transcripts by quantitative RT-PCR (qRT-PCR) is a sensitive method to detect neuroblastoma (NB) cells in the bone marrow (BM). However, its clinical utility following chemotherapy has not been thoroughly investigated. Procedures. TH transcripts in the BM were measured by qRT-PCR both at diagnosis and during the course of chemotherapy. The results were analyzed with respect to assay timing, tumor volume and histological findings. Results. TH transcripts were detected in 100% of BM aspirates at diagnosis in cases with concurrent tumor involvement in the BM section; however, the proportion of TH transcript positive BM aspirates in cases with concurrent tumor involvement in the BM section gradually decreased following chemotherapy (55.5% after three cycles, 28.6% after six cycles and 0% after nine or more cycles of chemotherapy). Decreased proportion of TH transcript positive BM aspirates was associated with reduced tumor volume in the BM and differentiation of tumors into mature forms during chemotherapy. When qRT-PCR was performed with both aspirated and biopsied tissue during chemotherapy, TH transcripts were detected in BM tissue not only in all of the histology-positive cases but also in some of the histology-negative cases, while the proportion of TH transcript positive BM aspirates was low, even in histology-positive cases. Conclusions. Measurement of TH transcripts in BM aspirates does not appear to be clinically useful during or after chemotherapy. Therefore, molecular monitoring of NB cells during or after chemotherapy using BM tissue is more optimal than testing on BM aspirates. Pediatr Blood Cancer 2010;55:273-278. (C) 2010 Wiley-Liss, Inc.