[Study of the expression of neural stem cell markers in neuroblastoma tumor samples and correlation with prognostic factors].
BACKGROUND
The existence of cancer stem cells (CSC) in neuroblastoma (NB) has been associated with the development of metastasis, resistance to chemotherapy and recurrence. Our objective is to analyze the expression of proliferation and differentiation markers of neural progenitor cells in NB samples, and to correlate this expression with clinical variables such as histology, genetics and response to conventional therapy.


METHODS
We performed a retrospective-experimental study with neuroblastoma samples obtained from biopsies or tumor resections between 2010-2012 in our Hospital. Fluorescence immunohistochemistry was used to analyze the expression of the different markers: CD44, CD74, CD133, tyrosine hydroxylase, endothelin receptors type A (ETA) and B (ETB), p75, nestina y and Phox2b, all of them related to neural stem cell biology. The level of expression of the markers was then correlated with clinical variables.


RESULTS
Nestin expression was positive in 72.2% of samples and ETA in 66.7%. PHOX2B and CD74 expression were lower, being positive in less than 30%. The markers CD44, ETB and PHOX2B were expressed in more aggressive tumors. ETA expression correlated significantly with unfavorable histology tumors (p= 0.01), N-myc amplification (p= 0.05) and recurrence/progression (p= 0.05).


CONCLUSIONS
The expression of CD44, ETB and ETA was associated with more aggressive tumors and poor prognostic factors. These markers are in the membrane of neural stem cells and may be useful to identify and isolate by flow cytometry CSCs of NB for the study of new therapeutic targets.
Servicio de Cirugía Pediátrica, Hospital Infantil Virgen del Rocío, Sevilla. yoli84mc@hotmail.com
Y
Y
Martínez-Criado
Servicio de Cirugía Pediátrica, Hospital Infantil Virgen del Rocío, Sevilla.
R
R
Cabello
Servicio de Cirugía Pediátrica, Hospital Infantil Virgen del Rocío, Sevilla.
I
I
Fernández-Pineda
Servicio de Oncología Pediátrica, Hospital Infantil Virgen del Rocío, Sevilla.
C
C
Márquez
Servicio de Oncología Pediátrica, Hospital Infantil Virgen del Rocío, Sevilla.
G
G
Ramírez
Servicio de Anatomía Patológica, Hospital Universitario Virgen del Rocío, Sevilla.
E
E
Rivas
Servicio de Anatomía Patológica, Hospital Universitario Virgen del Rocío, Sevilla.
M J
MJ
Robles
Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Dpto. de Fisiología Médica y Biofísica, Sevilla.
R
R
Pardal
Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Dpto. de Fisiología Médica y Biofísica, Sevilla.
F M
FM
Vega
D000008:Abdominal Neoplasms / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D002648:Child; D006801:Humans; D058953:Neural Stem Cells / Q000378:metabolism*; D009447:Neuroblastoma / Q000378:metabolism*; D011379:Prognosis; D012189:Retrospective Studies
D014408:Biomarkers, Tumor