title: Tubedown expression correlates with the differentiation status and aggressiveness of neuroblastic tumors.
abstract: OBJECTIVE
  The discovery and validation of new prognostic factors and further refinement of risk group stratification are needed to improve clinical interpretation of neuroblastoma. Our laboratory isolated and characterized a developmentally regulated gene named TUBEDOWN against which we have raised a monoclonal antibody (OE5). Tubedown becomes down-regulated postnatally yet remains strongly expressed in some neuroblastomas. The purpose of this study is to define the utility of Tubedown expression as a new measure of the differentiation status and aggressiveness of neuroblastic tumors.
  
  
  METHODS
  Tubedown protein expression was quantitatively assessed in neuroblastic tumors (neuroblastomas, ganglioneuroblastomas, and ganglioneuromas) and normal adrenal tissues using Western blot and OE5 immunohistochemistry. Regulation of Tubedown expression during retinoic acid-induced neuronal differentiation in neuroblastoma cell lines was assessed by Western blotting.
  
  
  RESULTS
  High levels of Tubedown expression are observed in tumors with significant neuroblastic component, unfavorable histopathology, advanced stage, high-risk group, and poor outcome. In contrast, more differentiated subsets of neuroblastic tumors, ganglioneuroblastomas with favorable histopathology and ganglioneuromas, express low levels of Tubedown. In vitro, marked retinoic acid-induced neuronal differentiation responses of neuroblastoma cells are associated with a significant decrease in Tubedown expression, whereas limited neuronal differentiation responses to retinoic acid were associated with little or no decrease in Tubedown expression.
  
  
  CONCLUSIONS
  Our results indicate that the levels of Tubedown expression are linked to the differentiation status and aggressiveness of neuroblastic tumors and represent an independent prognostic factor for neuroblastoma. Tubedown expression may be useful to more accurately define different neuroblastic tumor subsets and ultimately provide more adequate assessment and treatment for neuroblastoma patients.
authors.affiliation: Department of Medicine, Memorial University of Newfoundland, St. John's, Newfoundland, Canada.
authors.forename: Darryl T
authors.initials: DT
authors.lastname: Martin
authors.forename: Robert L
authors.initials: RL
authors.lastname: Gendron
authors.forename: Jason A
authors.initials: JA
authors.lastname: Jarzembowski
authors.forename: Arie
authors.initials: A
authors.lastname: Perry
authors.forename: Margaret H
authors.initials: MH
authors.lastname: Collins
authors.forename: Chitra
authors.initials: C
authors.lastname: Pushpanathan
authors.forename: Ewa
authors.initials: E
authors.lastname: Miskiewicz
authors.forename: Valerie P
authors.initials: VP
authors.lastname: Castle
authors.forename: Hélène
authors.initials: H
authors.lastname: Paradis
mesh_terms: D000123:Acetyltransferases / Q000096:biosynthesis*; D014408:Biomarkers, Tumor / Q000032:analysis*; D015153:Blotting, Western; D001932:Brain Neoplasms / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D009447:Neuroblastoma / Q000378:metabolism* / Q000473:pathology; D011379:Prognosis
chemical_list: D014408:Biomarkers, Tumor; D000123:Acetyltransferases