Measurement of Tyrosine Hydroxylase Expression in Bone Marrow Using Biopsied Tissue Instead of Aspirate
Measurement of Tyrosine Hydroxylase Expression in Bone Marrow Using Biopsied Tissue Instead of Aspirate
Abstract
Background: Molecular detection of tyrosine hydroxylase (TH) expression by quantitative RT-PCR is a sensitive method that allows detection of very low numbers of neuroblastoma (NB) cells in the bone marrow (BM). However, its clinical utility during chemotherapy has not been thoroughly investigated. Methods: TH expression in the BM was measured by quantitative RT-PCR both at diagnosis and during the course of chemotherapy. The TH expression rate and levels were analyzed with respect to assay timing, tumor volume, and histologic findings in concurrent BM sections. Results: TH expression in BM aspirate in cases with concurrent tumor involvement in the BM section was 100% at diagnosis; however, it gradually decreased during chemotherapy (55.5% after three cycles, 28.6% after six cycles, and 0% after nine or more cycles of chemotherapy). A decreased detection rate in aspirates despite concurrent tumor involvement in the BM section was associated with both reduced tumor volume in the BM and differentiation of the tumor into a mature form during chemotherapy. When quantitative RT-PCR was performed with both aspirate and biopsied tissue during chemotherapy, TH expression in BM tissue was positive not only in all histology-positive cases but also in some histology-negative cases, while TH expression in BM aspirate samples was low, even in histology-positive cases. Conclusions: Measurement of TH expression in BM aspirate is not useful during or after chemotherapy. Therefore, molecular monitoring of NB cells during or after chemotherapy should be performed using BM tissue rather than BM aspirate.