Plasma neuropeptide Y of children with neuroblastoma in relation to stage, age and prognosis, and tissue neuropeptide Y.

The objective of this study was to relate plasma neuropeptide Y (NPY) concentrations of patients with neuroblastoma with the stage of the disease, the patients' age, the prognosis, the tumor mRNA expression and with the effect on tumor cell proliferation. Plasma NPY of 85 patients with neuroblastoma was measured by radioimmunoassay. The patients' median age was 18 months (range, three weeks-12 years). Ten children with childhood tumors that did not affect neurological or neuroendocrine structures and ten healthy children served as control groups. NPY mRNA expression in neuroblastoma tissue was assessed by Northern blot analysis. Proliferation of neuroblastoma cells (SK-N-MC and CHP 234) was evaluated by 5-bromo-2'-deoxyuridine incorporation during DNA synthesis in vitro. Plasma NPY levels were significantly higher in stage 3 (p < 0.05), 4 (p < 0.001) and 4S (p < 0.05) patients than in both control groups. Plasma levels above 8 pmol/l were only seen in stages 2 (17%), 3 (32%), 4 (45%) and 4S (44%). Seven of the 12 patients (58%) who died had NPY levels above 8 pmol/l (vs. 29% in survivors; p = 0.05). In patients with longer follow-up monitoring, relapse coincided with increasing NPY levels. There was no relationship between the patients' age and their plasma NPY concentrations (r = 0.08; p = 0.49). No relation was found between NPY mRNA expression in tumor tissue and NPY plasma concentrations of the ten patients (r = 0.08; p = 0.81). NPY in the supernatant of neuroblastoma cells did not alter the 5-bromo-2'-deoxyuridine incorporation during DNA synthesis. In summary, NPY plasma concentrations in patients with neuroblastoma relate to the stage of the disease. The relation to the prognosis is at the threshold of significance. No relation between tissue and plasma NPY, nor any effect of NPY on proliferation of tumor cells was found.