Urinary dopamine/noradrenaline and dopamine/vanillylmandelic acid ratios as a reflection of different biology of adrenergic clones in children's neuroblastic tumors

Prognostic significance of biochemical heterogeneity of catecholaminergic clones in neuroblastoma

“…Moreover, surviving children with stage IV neuroblastoma presented with tumors composed primarily of cells without the DBH block. Present data confirm earlier reports and suggest a block or reduced activity of DBH in lessdifferentiated tumors [14,15], leading to a conclusion that differential production of neurotransmitters in the population of tumor cells may be partially explained in terms of tumor heterogeneity, which determines the clinical course of the disease. [11][12][13][14].…”

“…However, these conclusions were based on a common test of the metabolite levels in a 24-hour urine collection, which does not take into account diurnal fluctuation of catecholamine excretion. Dopamine and DA/NAd proportions, based on direct measurement of catecholamines related to DBH activity, are also recognized as prognostically relevant risk factors [14,15]. An inverse correlation between high DA levels and survival was found in pediatric patients [13,20].…”

“…The normalized values were used to compute the proportions for DA/NAd and DA/VMA. Based on the highest reported values for children with ganglioneuroma and neuroblastoma tumors in stages I and II [14], the value of 1.8 was considered normal for both DA/NAd and DA/VMA. Tumor advancement stages were assessed as described [19].…”

“…The prognostic value of tumor heterogeneity has not been described before. This study addressed these issues in an analysis of historical data from studies over 20 years in a single clinical institution, expanding earlier work with a smaller cohort of patients [14]. To test the hypothesis that the ratios of DA/NAd and DA/VMA reflect the composition of adrenergic clones and tumor heterogeneity, we investigated urinary DA/NAd as well as DA/VMA ratios suggestive of DBH activity and the prognostic values thereof.…”

Identification of Novel Prognostic Markers in Relapsing Localized Resectable Neuroblastoma

“…urine are diagnostic in NB (Brodeur et al, 1993) Furthermore, some authors observed an association of unfavorable disease with low VMA levels and/or high DA levels (Barontini et al, 1993;Izbicki et al, 1991;Laug et al, 1978;Nakagawara et al, 1990;O'Meara et al, 1994); however, only relatively small numbers of patients were analyzed. In a recent study (Strenger et al, 2007), the levels of urinary catecholamines have been correlated to stages (1, 2, 3, 4, 4s), biological features, and prognosis in 114 NB patients.…”