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High level of apoptosis and low AKT activation in mass screening as opposed to standard neuroblastoma.

Sartelet H, Ohta S, Barrette S, Rougemont AL, Brevet M, Regairaz M, Harvey I, Bernard C, Fabre M, Gaboury L, Oligny LL, Bosq J, Valteau-Couanet D, Vassal G

Department of Pathology, CHU Sainte Justine Montreal, Montreal, Quebec, Canada. herve.sartelet.hsj@ssss.gouv.qc.ca

AIMS: 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. METHODS AND 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.

Histopathology 2010;56(5):607-16.

Pubmed ID: 20459571

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