High level of apoptosis and low AKT activation in mass screening as opposed to standard neuroblastoma.
OBJECTIVE
Neuroblastoma is a paediatric solid tumour with a poor outcome except in children <1 year old. Based on catecholamine urinary excretion, mass screening (MS) programmes have been organized but failed to decrease the mortality of this tumour. To test the hypotheses of a spontaneous maturation/differentiation or regression, the levels of poly (ADP-ribose) polymerase (PARP)-1, an early apoptosis marker, of PhosphoAKT, a major apoptosis inhibitor, and of maturation/differentiation were compared in standard and in MS neuroblastomas.


RESULTS
We performed a case-control study of 55 primary tumours and 21 metastases of MS neuroblastomas. Matched controls were standard unscreened neuroblastomas and were paired according to age, stage, and MYCN amplification. The tumours were included in tissue microarrays. Immunohistochemical staining was performed using antibodies against, AKT, phosphoAKT, TRKB and PARP-1. The expression of PARP-1 and that of phosphoAKT were significantly higher in standard than in MS neuroblastomas independently of age and stage of the tumour. PhosphoAKT and PARP-1 expression was significantly correlated in both tumours.


CONCLUSIONS
These data suggest that the better prognosis of patients with MS neuroblastomas compared with classical neuroblastomas was secondary to spontaneous tumour regression mediated by higher levels of apoptosis associated with low activation of AKT.
Sartelet
Hervé
H
Department of Pathology, CHU Sainte Justine Montreal, Montreal, Quebec, Canada. herve.sartelet.hsj@ssss.gouv.qc.ca
Ohta
Shigeru
S
Barrette
Stephane
S
Rougemont
Anne-Laure
AL
Brevet
Marie
M
Regairaz
Marie
M
Harvey
Isabelle
I
Bernard
Chantal
C
Fabre
Monique
M
Gaboury
Louis
L
Oligny
Luc L
LL
Bosq
Jacques
J
Valteau-Couanet
Dominique
D
Vassal
Gilles
G
D000818:Animals; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000378:metabolism; D002170:Canada / Q000453:epidemiology; D016022:Case-Control Studies; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D007564:Japan / Q000453:epidemiology; D007680:Kidney Neoplasms / Q000453:epidemiology / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008403:Mass Screening; D051379:Mice; D008819:Mice, Nude; D009367:Neoplasm Staging; D009447:Neuroblastoma / Q000453:epidemiology / Q000378:metabolism / Q000556:secondary*; D010766:Phosphorylation; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000032:analysis / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015996:Survival Rate; D046888:Tissue Array Analysis
D014408:Biomarkers, Tumor; C499320:PARP1 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases; D051057:Proto-Oncogene Proteins c-akt