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Pediatric brainstem gangliogliomas show overexpression of neuropeptide prepronociceptin (PNOC) by microarray and immunohistochemistry
Author(s) -
Chan Michael H.,
KleinschmidtDeMasters B.K.,
Donson Andrew M.,
Birks Diane K.,
Foreman Nicholas K.,
Rush Sarah Z.
Publication year - 2012
Publication title -
pediatric blood and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.116
H-Index - 105
eISSN - 1545-5017
pISSN - 1545-5009
DOI - 10.1002/pbc.24232
Subject(s) - medicine , brainstem , immunohistochemistry , neuropeptide , microarray , pathology , gene , biology , gene expression , genetics , receptor
Background Gangliogliomas (GGs) primary to brainstem are rare, with the overwhelming majority of GGs occurring in supratentorial, especially temporal lobe, locations. A less favorable prognosis exists for brainstem GGs, despite their usually identical WHO grade I status. Few large clinical series, and limited biological information, exists on these tumors, especially gene expression. Procedure Seven pediatric brainstem GGs, all with classic histological features, seen at our institution since 2000 were identified. Frozen section material was available for gene expression microarray profiling from five of seven brainstem GGs and compared with that from three non‐brainstem pediatric GGs. Results Significant upregulation of a number of genes was identified, most of which were involved in pathways of neural signaling, embryonic development, and pattern specification in pediatric brainstem GGs compared to non‐brainstem. The single largest upregulated gene was a 256‐fold increase in the expression of the neuropeptide prepronociceptin (PNOC); the protein product of this gene has been implicated in neuronal growth. Overexpression was validated by Western blot and by immunohistochemistry (IHC). Strong IHC expression of PNOC was seen in neoplastic neurons of 7/7 brainstem GGs, but was significantly weaker in non‐brainstem GGs, and completely negative in normal pediatric autopsy brainstem controls. Conclusions PNOC IHC was often superior to IHC for NeuN, synaptophysin, or neurofilament for highlighting neoplastic neurons. Pediatr Blood Cancer 2012; 59: 1173–1179. © 2012 Wiley Periodicals, Inc.