IGF2 expression is a marker for paraganglionic/SIF cell differentiation in neuroblastoma.

Abstract

Neuroblastoma is a childhood tumor of the sympathetic nervous system. Observations in the Beckwith-Wiedemann syndrome suggest that sympathetic embryonal cells with an abundant expression of the insulin-like growth factor 2 gene (IGF2) may be involved in the genesis of low-malignant infant neuroblastomas. We have therefore compared the cell type-specific IGF2 expression of the human sympathetic nervous system during early development with that of neuroblastoma. An abundant expression in normal sympathetic tissue was specific to extra-adrenal chromaffin cells, ie, paraganglia and small intensely fluorescent (SIF) cells, whereas sympathetic neuronal cells were IGF2-negative. A subpopulation of neuroblastomas expressed IGF2, which correlated with an early age at diagnosis, an extra-adrenal tumor origin, and severe hemodynamic signs of catecholamine secretion. Histologically IGF2-expressing tumors displayed a lobular growth pattern, and expression was restricted to the most mature and least proliferative cells. Typically, these cells were morphologically and histochemically similar to paraganglia/SIF cells and formed distinct ring-like zones in the center of the lobules around a core of apoptosis-like tumor cells. The similarities found between IGF2-expressing neuroblastoma cells and paraganglia/SIF cells in terms of histological features, anatomical origin, and age-dependent growth suggest a paraganglionic/SIF cell lineage of most infant tumors and also of extra-adrenal tumors diagnosed after infancy. Furthermore, since paraganglia/SIF cells undergo postnatal involution, the same cellular mechanism may be responsible for spontaneous regression in infant neuroblastoma.

• Authors: F Hedborg, R Ohlsson, B Sandstedt, L Grimelius, J C Hoehner, S Pählman
• Journal: The American journal of pathology (Am J Pathol) Vol. 146 Issue 4 Pg. 833-47 (Apr 1995) ISSN: 0002-9440 [Print] United States
• PMID: 7717451 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers, Tumor
• Chromogranin A
• Chromogranins
• Insulin-Like Growth Factor II

Topics

• Biomarkers, Tumor (analysis)
• Cell Differentiation
• Child
• Child, Preschool
• Chromogranin A
• Chromogranins (analysis)
• Embryonic and Fetal Development (genetics)
• Ganglioneuroblastoma (chemistry, genetics)
• Ganglioneuroma (chemistry, genetics)
• Humans
• Immunoenzyme Techniques
• In Situ Hybridization
• Infant
• Infant, Newborn
• Insulin-Like Growth Factor II (analysis)
• Neuroblastoma (chemistry, genetics, pathology)
• Paraganglia, Chromaffin (pathology)
• Sympathetic Nervous System (embryology)