SOMATOSTATIN IN NEUROBLASTOMA AND GANGLIONEUROMA

Neuroblastoma, a childhood tumour of the sympathetic nervous system, m ay in some cases differentiate to a benign ganglioneuroma or regress d ue to apoptosis. Somatostatin may inhibit neuroblastoma growth and ind uce apoptosis in vitro and was therefore investigated. Using a radioim munoassay, we found that all ganglioneuromas contained high somatostat in concentrations (> 16 pmol/g), significantly higher than neuroblasto mas (n = 117, median 2.8 pmol/g), healthy adrenals, Wilms' tumours, ph aeochromocytomas and other neuroendocrine tumours (P < 0.001). Neurobl astomas contained more somatostatin than control tumours (P < 0.001-0. 05). Neuroblastomas amplified for the MYCN oncogene contained less som atostatin than non-amplified tumours (1.2 pmol/g versus 4.0 pmol/g, re spectively; P=0.026). In a clinically unfavourable neuroblastoma subse t (age > 12 months, stage 3 or 4) 16 children with high concentrations of somatostatin in primary tumours had a better prognosis than 23 wit h low somatostatin (46.7% versus 0% survival at 5 years, P < 0.005). S cintigraphy using In-111-pentetreotide identified tumours expressing h igh-affinity somatostatin receptors in vivo. However, no significant c orrelation was found between somatostatin receptor expression and pept ide content in 15 tumours. Similarly, human SH-SY5Y neuroblastoma xeno grafts grown in nude rats showed low somatostatin concentrations, but were positive for somatostatin receptor scintigraphy. Treatment of the se rats with the somatostatin analogue octreotide seemed to upregulate in vivo receptor expression of somatostatin and vasoactive intestinal peptide more effectively than 13-cis retinoic acid. In conclusion, so matostatin in neuroblastoma is associated with differentiation to beni gn ganglioneuromas in vivo and favourable outcome in advanced tumours. Furthermore, somatostatin receptor scintigraphy may identify tumours with high-affinity receptors in children that might benefit from targe ted therapy using synthetic somatostatin analogues. (C) 1997 Published by Elsevier Science Ltd.