Circulating neuroblastoma cells detected by reverse transcriptase polymerase chain reaction for tyrosine hydroxylase mRNA are an independent poor prognostic indicator in stage 4 neuroblastoma in children over 1 year.
OBJECTIVE
In this prospective, multicenter study, the independent prognostic power of neuroblastoma cells detected by reverse transcriptase polymerase chain reaction (RT-PCR) for tyrosine hydroxylase (TH) mRNA was evaluated.


METHODS
The clinical significance of disease detected by RT-PCR in peripheral blood from children at diagnosis was compared with established prognostic markers [ie, age, lactate dehydrogenase (LDH), neuron-specific enolase, ferritin, and MYCN gene amplification] by multivariate analysis. The value of disease detection by RT-PCR during treatment and follow-up was also examined.


RESULTS
TH mRNA was detected in peripheral blood from 33 of 49 (67%) children with stage 4 neuroblastoma > 1 year old at diagnosis and was a significant predictive factor for overall survival [hazard ratio (HR) = 2.40, 95% confidence interval (CI) 1.19 to 4.84, P =.014) and event-free survival (HR = 2.09, 95% CI 1.06 to 4.17, P =.034) in a multivariate analysis. Detection of disease in blood from clinically disease-free children was related to increased risk of death (HR 2.54, 95% CI 1.42 to 4.55, P =.0014).


CONCLUSIONS
TH mRNA in peripheral blood of children with neuroblastoma is a poor prognostic indicator, reflecting the propensity for dissemination via the bloodstream. When combined with a serum LDH > 1500 IU/L, this is the most powerful poor prognostic model at diagnosis for children > 1 year old with stage 4 disease. The detection of TH mRNA in peripheral blood from clinically disease-free children is related to increased risk of relapse and death.
Candlelighter's Children's Cancer Research Laboratory, Imperial Cancer Research Fund Cancer Medicine Research Unit, St James's University Hospital, Leeds, United Kingdom. s.a.burchill@leeds.ac.uk
S A
SA
Burchill
I J
IJ
Lewis
K R
KR
Abrams
R
R
Riley
J
J
Imeson
A D
AD
Pearson
R
R
Pinkerton
P
P
Selby
D000367:Age Factors; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D009360:Neoplastic Cells, Circulating; D009447:Neuroblastoma / Q000235:genetics / Q000473:pathology*; D011379:Prognosis; D011446:Prospective Studies; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016019:Survival Analysis; D014446:Tyrosine 3-Monooxygenase / Q000032:analysis / Q000096:biosynthesis / Q000235:genetics*
D012333:RNA, Messenger; D014446:Tyrosine 3-Monooxygenase