Faculty Collaboration Database

Tubedown expression correlates with the differentiation status and aggressiveness of neuroblastic tumors. Clin Cancer Res 2007 Mar 01;13(5):1480-7

Date

03/03/2007

Pubmed ID

17332292

DOI

10.1158/1078-0432.CCR-06-1716

Scopus ID

2-s2.0-33947424032 (requires institutional sign-in at Scopus site)   13 Citations

Abstract

PURPOSE: 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.

EXPERIMENTAL DESIGN: 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.

Author List

Martin DT, Gendron RL, Jarzembowski JA, Perry A, Collins MH, Pushpanathan C, Miskiewicz E, Castle VP, Paradis H

Author

Jason A. Jarzembowski MD, PhD Sr Associate Dean, CEO CSG, Professor in the Pathology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Acetyltransferases
Biomarkers, Tumor
Blotting, Western
Brain Neoplasms
Humans
Immunohistochemistry
In Situ Hybridization, Fluorescence
Neuroblastoma
Prognosis