Clinical implications of minimal disease in the bone marrow and peripheral blood in neuroblastoma

J Pediatr Surg. 2000 Oct;35(10):1415-20. doi: 10.1053/jpsu.2000.16403.


Purpose: In patients with neuroblastoma (NB), minimal disease (MD) in bone marrow (BM) and peripheral blood (PB) is thought to play an important role in metastasis. The current study was designed to evaluate the clinical implications of the detection of MD in NB at the initial diagnosis.

Methods: Expression of the neuroendocrine protein gene product 9.5 (PGP9.5) and tyrosine hydroxylase (TH) mRNA in BM and PB obtained from 18 patients with NB was investigated by reverse transcriptase-polymerase chain reaction (RT-PCR).

Results: MD was detected in the BM obtained from 4 of 14 localized NB patients and also in the PB from 2. However, it was found also in both the BM and PB obtained from all 4 patients with metastatic NB. Two of the 4 MD-positive patients with localized NB had metastatic recurrence after a complete tumor excision. They also had unfavorable biological prognostic factors compared with the other 2 who did not have recurrent disease.

Conclusion: MD detected by RT-PCR in the BM and the PB of patients with NB thus suggests a risk for metastatic disease, which in association with other unfavorable biological features may indicate a poor prognosis.

MeSH terms

  • Adolescent
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Bone Marrow / metabolism
  • Bone Marrow / pathology*
  • Child
  • Flow Cytometry
  • Gene Expression
  • Humans
  • Immunohistochemistry
  • Neoplasm Staging
  • Neoplasm, Residual / blood
  • Neoplasm, Residual / diagnosis
  • Neoplastic Cells, Circulating* / metabolism
  • Neoplastic Cells, Circulating* / pathology
  • Nerve Tissue Proteins / genetics*
  • Nerve Tissue Proteins / metabolism
  • Neuroblastoma / blood*
  • Neuroblastoma / pathology*
  • Ploidies
  • Prognosis
  • RNA, Messenger / analysis
  • Reverse Transcriptase Polymerase Chain Reaction
  • Thiolester Hydrolases / genetics*
  • Thiolester Hydrolases / metabolism
  • Tumor Cells, Cultured
  • Tyrosine 3-Monooxygenase / genetics*
  • Tyrosine 3-Monooxygenase / metabolism
  • Ubiquitin Thiolesterase


  • Nerve Tissue Proteins
  • RNA, Messenger
  • Tyrosine 3-Monooxygenase
  • Thiolester Hydrolases
  • Ubiquitin Thiolesterase