TY - JOUR
T1 - Expression of the neuron-specific protein CHD5 is an independent marker of outcome in neuroblastoma
AU - Garcia, Idoia
AU - Mayol, Gemma
AU - Rodríguez, Eva
AU - Suñol, Mariona
AU - Gershon, Timothy R.
AU - Ríos, José
AU - Cheung, Nai Kong V.
AU - Kieran, Mark W.
AU - George, Rani E.
AU - Perez-Atayde, Antonio R.
AU - Casala, Carla
AU - Galván, Patricia
AU - de Torres, Carmen
AU - Mora, Jaume
AU - Lavarino, Cinzia
N1 - Funding Information:
Authors thank Dr. B. Spengler (Fordham University, New York) and Dr. N.K.V. Cheung (MSKCC, New York) for annotated NB cell lines; the Neural Tissue Bank (Hospital Clínic, Barcelona) for normal brain samples and the Department of Audiovisual Systems (HSJD, Barcelona) for technical assistance. This study was supported by grants from the Spanish Ministry of Health (PI070286), Spanish Society against Cancer (Asociación Española Contra el Cáncer, 2007), the Catalan government (2005SGR00605; 2006FI00404), and the generous donations from Margarita del Pozo and Alicia Pueyo Foundations.
PY - 2010/10/15
Y1 - 2010/10/15
N2 - Background: The chromodomain, helicase DNA-binding protein 5 (CHD5) is a potential tumor suppressor gene located on chromosome 1p36, a region recurrently deleted in high risk neuroblastoma (NB). Previous data have shown that CHD5 mRNA is present in normal neural tissues and in low risk NB, nevertheless, the distribution of CHD5 protein has not been explored. The aim of this study was to investigate CHD5 protein expression as an immunohistochemical marker of outcome in NB. With this purpose, CHD5 protein expression was analyzed in normal neural tissues and neuroblastic tumors (NTs). CHD5 gene and protein expression was reexamined after induction chemotherapy in a subset of high risk tumors to identify potential changes reflecting tumor response.Results: We provide evidence that CHD5 is a neuron-specific protein, absent in glial cells, with diverse expression amongst neuron types. Within NTs, CHD5 immunoreactivity was found restricted to differentiating neuroblasts and ganglion-like cells, and absent in undifferentiated neuroblasts and stromal Schwann cells. Correlation between protein and mRNA levels was found, suggesting transcriptional regulation of CHD5. An immunohistochemical analysis of 90 primary NTs highlighted a strong association of CHD5 expression with favorable prognostic variables (age at diagnosis <12 months, low clinical stage, and favorable histology; P < 0.001 for all), overall survival (OS) (P < 0.001) and event-free survival (EFS) (P < 0.001). Multivariate analysis showed that CHD5 prognostic value is independent of other clinical and biologically relevant parameters, and could therefore represent a marker of outcome in NB that can be tested by conventional immunohistochemistry. The prognostic value of CHD5 was confirmed in an independent, blinded set of 32 NB tumors (P < 0.001).Reactivation of CHD5 expression after induction chemotherapy was observed mainly in those high risk tumors with induced tumor cell differentiation features. Remarkably, these NB tumors showed good clinical response and prolonged patient survival.Conclusions: The neuron-specific protein CHD5 may represent a marker of outcome in NB that can be tested by conventional immunohistochemistry. Re-establishment of CHD5 expression induced by chemotherapy could be a surrogate marker of treatment response. © 2010 Garcia et al; licensee BioMed Central Ltd.
AB - Background: The chromodomain, helicase DNA-binding protein 5 (CHD5) is a potential tumor suppressor gene located on chromosome 1p36, a region recurrently deleted in high risk neuroblastoma (NB). Previous data have shown that CHD5 mRNA is present in normal neural tissues and in low risk NB, nevertheless, the distribution of CHD5 protein has not been explored. The aim of this study was to investigate CHD5 protein expression as an immunohistochemical marker of outcome in NB. With this purpose, CHD5 protein expression was analyzed in normal neural tissues and neuroblastic tumors (NTs). CHD5 gene and protein expression was reexamined after induction chemotherapy in a subset of high risk tumors to identify potential changes reflecting tumor response.Results: We provide evidence that CHD5 is a neuron-specific protein, absent in glial cells, with diverse expression amongst neuron types. Within NTs, CHD5 immunoreactivity was found restricted to differentiating neuroblasts and ganglion-like cells, and absent in undifferentiated neuroblasts and stromal Schwann cells. Correlation between protein and mRNA levels was found, suggesting transcriptional regulation of CHD5. An immunohistochemical analysis of 90 primary NTs highlighted a strong association of CHD5 expression with favorable prognostic variables (age at diagnosis <12 months, low clinical stage, and favorable histology; P < 0.001 for all), overall survival (OS) (P < 0.001) and event-free survival (EFS) (P < 0.001). Multivariate analysis showed that CHD5 prognostic value is independent of other clinical and biologically relevant parameters, and could therefore represent a marker of outcome in NB that can be tested by conventional immunohistochemistry. The prognostic value of CHD5 was confirmed in an independent, blinded set of 32 NB tumors (P < 0.001).Reactivation of CHD5 expression after induction chemotherapy was observed mainly in those high risk tumors with induced tumor cell differentiation features. Remarkably, these NB tumors showed good clinical response and prolonged patient survival.Conclusions: The neuron-specific protein CHD5 may represent a marker of outcome in NB that can be tested by conventional immunohistochemistry. Re-establishment of CHD5 expression induced by chemotherapy could be a surrogate marker of treatment response. © 2010 Garcia et al; licensee BioMed Central Ltd.
UR - https://www.scopus.com/pages/publications/77957907502
U2 - 10.1186/1476-4598-9-277
DO - 10.1186/1476-4598-9-277
M3 - Article
C2 - 20950435
SN - 1476-4598
VL - 9
JO - Molecular Cancer
JF - Molecular Cancer
M1 - 277
ER -
