Multiple target molecular monitoring of bone marrow and peripheral blood samples from patients with localized neuroblastoma and healthy donors.
BACKGROUND
Multiple target molecular monitoring of minimal residual disease in neuroblastoma (NB) patients may increase sensitivity and overcome tumor heterogeneity. However, multiple target analysis is costly and time consuming, thus improvement with respect to single target monitoring needs to be achieved.


METHODS
Italian patients with localized NB were evaluated at diagnosis for TH, GD2-s, DDC, DCX, ELAV-4, STX, and Phox2b mRNA expressions. Patients with metastatic NB were tested as positive controls, together with NB primary tumors and cell lines, while healthy donors were tested as negative controls.


RESULTS
All NB-related markers but Phox2b were expressed in healthy donors, and in a high percentage of patients with localized NB without association with clinical events. The introduction of cut-off levels increased marker specificity, although the percentage of positive results was only slightly modified. While TH positivity in PB samples significantly associated with a worse prognosis, a paradox association was found for GD2-s mRNA expression. No correlation and agreement between quantitative and qualitative results obtained with the two assays were found. In the set of samples tested for all markers, no pattern of expression was found to be associated with a specific clinical situation.


CONCLUSIONS
These findings suggest that positive molecular results may not reflect the presence of disease, and that correlation among different markers is small in condition of low tumor burden. Thus, to reduce cost and amount of precious samples, in addition to TH, whose prognostic value was confirmed, only Phox2b warrants further evaluation in multi-center, prospective studies for high risk patients.
Laboratory of Oncology, Gaslini Institute, Genoa, Italy. mariavaleriacorrias@ospedale-gaslini.ge.it
Maria Valeria
MV
Corrias
Riccardo
R
Haupt
Barbara
B
Carlini
Enrico
E
Cappelli
Stefano
S
Giardino
Gino
G
Tripodi
Gian Paolo
GP
Tonini
Alberto
A
Garaventa
Vito
V
Pistoia
Angela
A
Pistorio
D014408:Biomarkers, Tumor / Q000097:blood*; D001853:Bone Marrow / Q000378:metabolism* / Q000473:pathology; D016022:Case-Control Studies; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D018365:Neoplasm, Residual / Q000097:blood* / Q000473:pathology; D009447:Neuroblastoma / Q000097:blood* / Q000473:pathology; D015996:Survival Rate; D016896:Treatment Outcome
D014408:Biomarkers, Tumor