title: Somatostatin in neuroblastoma and ganglioneuroma.
abstract: Neuroblastoma, a childhood tumour of the sympathetic nervous system, may in some cases differentiate to a benign ganglioneuroma or regress due to apoptosis. Somatostatin may inhibit neuroblastoma growth and induce apoptosis in vitro and was therefore investigated. Using a radioimmunoassay, we found that all ganglioneuromas contained high somatostatin concentrations (> 16 pmol/g), significantly higher than neuroblastomas (n = 117, median 2.8 pmol/g), healthy adrenals, Wilms' tumours, phaeochromocytomas and other neuroendocrine tumours (P < 0.001). Neuroblastomas contained more somatostatin than control tumours (P < 0.001-0.05). Neuroblastomas amplified for the MYCN oncogene contained less somatostatin than non-amplified tumours (1.2 pmol/g versus 4.0 pmol/g, respectively; P = 0.026). In a clinically unfavourable neuroblastoma subset (age > 12 months, stage 3 or 4) 16 children with high concentrations of somatostatin in primary tumours had a better prognosis than 23 with low somatostatin (46.7% versus 0% survival at 5 years, P < 0.005). Scintigraphy using 111In-pentetreotide identified tumours expressing high-affinity somatostatin receptors in vivo. However, no significant correlation was found between somatostatin receptor expression and peptide content in 15 tumours. Similarly, human SH-SY5Y neuroblastoma xenografts grown in nude rats showed low somatostatin concentrations, but were positive for somatostatin receptor scintigraphy. Treatment of these 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, somatostatin in neuroblastoma is associated with differentiation to benign 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 targeted therapy using synthetic somatostatin analogues.
authors.affiliation: Dept. of Woman and Child Health, Karolinska Institute, Karolinska Hospital, Stockholm, Sweden.
authors.forename: P
authors.initials: P
authors.lastname: Kogner
authors.forename: P
authors.initials: P
authors.lastname: Borgström
authors.forename: P
authors.initials: P
authors.lastname: Bjellerup
authors.forename: F H
authors.initials: FH
authors.lastname: Schilling
authors.forename: E
authors.initials: E
authors.lastname: Refai
authors.forename: C
authors.initials: C
authors.lastname: Jonsson
authors.forename: C
authors.initials: C
authors.lastname: Dominici
authors.forename: E
authors.initials: E
authors.lastname: Wassberg
authors.forename: H
authors.initials: H
authors.lastname: Bihl
authors.forename: H
authors.initials: H
authors.lastname: Jacobsson
authors.forename: E
authors.initials: E
authors.lastname: Theodorsson
authors.forename: M
authors.initials: M
authors.lastname: Hassan
mesh_terms: D000818:Animals; D005500:Follow-Up Studies; D005729:Ganglioneuroma / Q000378:metabolism*; D005784:Gene Amplification; D016259:Genes, myc / Q000235:genetics; D006801:Humans; D007223:Infant; D009367:Neoplasm Staging; D009447:Neuroblastoma / Q000378:metabolism*; D015282:Octreotide / Q000378:metabolism; D051381:Rats; D011923:Rats, Nude; D017481:Receptors, Somatostatin / Q000378:metabolism; D013004:Somatostatin / Q000378:metabolism*; D015996:Survival Rate; D014183:Transplantation, Heterologous; D014212:Tretinoin / Q000378:metabolism; D014660:Vasoactive Intestinal Peptide / Q000378:metabolism
chemical_list: D017481:Receptors, Somatostatin; D014660:Vasoactive Intestinal Peptide; D013004:Somatostatin; D014212:Tretinoin; D015282:Octreotide