IN-VIVO SPONTANEOUS NEURONAL TO NEUROENDOCRINE LINEAGE CONVERSION IN A SUBSET OF NEUROBLASTOMAS

Neuroblastoma is an embryonal tumor derived from the sympathetic nervo us system. Although all neuroblastomas have a neuronal character, a su bset of tumors also show evidence of extra-adrenal neuroendocrine diff erentiation in discrete cell layers. A characterization of the cells o f the developing human sympathetic nervous system was performed, ident ifying growth-associated protein-43, neuropeptide tyrosine, and Bcl-2 as marker genes for sympathetic neurons. Whereas all neuroblastomas ex press growth-associated protein-43, neuropeptide tyrosine, and Bcl-2, tumors with differentiating cells with neuroendocrine features express ed there genes only in the morphologically immature, proliferating cel ls. Thus, with neuroendocrine tumor cell differentiation, neuronal mar ker gene expression vanished and proliferation ceased and was succeede d by expression of chromogranin A/B and insulin-like growth factor-2, markers of neuroendocrine chromaffin differentiation. These tumors app ear to provide examples of spontaneous lineage conversion from a neuro nal to a neuroendocrine phenotype.