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American Journal of Pathology, Vol 150, 107-117, Copyright © 1997 by American Society for Investigative Pathology

REGULAR ARTICLES

In vivo spontaneous neuronal to neuroendocrine lineage conversion in a subset of neuroblastomas

C Gestblom, JC Hoehner, F Hedborg, B Sandstedt and S Pahlman
Department of Medicine, Lund University, Malmo University Hospital, Sweden.

Neuroblastoma is an embryonal tumor derived from the sympathetic nervous system. Although all neuroblastomas have a neuronal character, a subset of tumors also show evidence of extra-adrenal neuroendocrine differentiation in discrete cell layers. A characterization of the cells of the developing human sympathetic nervous system was performed, identifying growth-associated protein-43, neuropeptide tyrosine, and Bcl-2 as marker genes for sympathetic neurons. Whereas all neuroblastomas express growth-associated protein-43, neuropeptide tyrosine, and Bcl-2, tumors with differentiating cells with neuroendocrine features expressed these genes only in the morphologically immature, proliferating cells. Thus, with neuroendocrine tumor cell differentiation, neuronal marker gene expression vanished and proliferation ceased and was succeeded by expression of chromogranin A/B and insulin-like growth factor-2, markers of neuroendocrine chromaffin differentiation. These tumors appear to provide examples of spontaneous lineage conversion from a neuronal to a neuroendocrine phenotype.

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