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Developmental
Gene Expression of Sympathetic Nervous System Tumors Reflects Their Histogenesis
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Jeff C. Hoehner,
Fredrik Hedborg, Lars Eriksson, Bengt Sandstedt, Lars Grimelius, Leif Olsen,
and Sven Pahlman |
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Departments
of Pathology (JCH, FH, LE, LG), Pediatric Surgery (JCH, LO), and Pediatrics
(FH), Uppsala University Hospital, Uppsala; Department of Pediatric Pathology
(BS), Karolinska Hospital, Stockholm; and Department of Laboratory Medicine
(SP), Lund University, Malmo, Sweden |
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Comparisons of the developing
human sympathetic nervous system (SNS) to tumors presumed to derive from
these cells may suggest tumor progenitors and predict tumor biologic behavior.
Classic neuroblastoma (NB) and its more highly differentiated stroma-rich
subtypes, extra-adrenal sympathetic paraganglioma, and pheochromocytoma
were examined for the presence of the developmentally characterized gene
products NSE, S-100, CD44, Bcl-2, HNK-1, PNMT, TrkA, IGF2, and tyrosine
hydroxylase. The marker gene expression profiles of these tumors were compared
with those similarly determined for a number of normal prenatal and postnatal
human SNS cell types. Sympathetic paraganglioma, pheochromocytoma, and stroma-rich
NB display marker expression profiles mimicking those of childhood sympathetic
paraganglia, adrenal chromaffin cells, and sympathetic neurons, respectively.
A selection of differentiating, extra-adrenal NB tumors with prognostically
favorable features possess marker gene expression profiles paralleling that
observed for fetal extra-adrenal sympathetic paraganglia/small intensely
fluorescent cells. In contrast, undifferentiated, clinically aggressive
NB tumors manifest characteristics mirroring that of embryonic/early fetal
sympathetic neuroblasts of sympathetic ganglia and of the adrenal gland.
These findings suggest that clinical features, such as primary tumor location
and age at diagnosis, provide prognostic information for NB patients by
virtue of the existence and biology of the presumed tumor progenitor cell
type. |
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