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

• Published in: Histopathology Vol. 56; no. 5; pp. 607 - 616
• Main Authors: Sartelet, Hervé, Ohta, Shigeru, Barrette, Stephane, Rougemont, Anne-Laure, Brevet, Marie, Regairaz, Marie, Harvey, Isabelle, Bernard, Chantal, Fabre, Monique, Gaboury, Louis, Oligny, Luc L, Bosq, Jacques, Valteau-Couanet, Dominique, Vassal, Gilles
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01-04-2010; Blackwell
• Subjects: AKT; Animals; Apoptosis; Biological and medical sciences; Biomarkers, Tumor - metabolism; Canada - epidemiology; Case-Control Studies; Child, Preschool; Female; Humans; Infant; Investigative techniques, diagnostic techniques (general aspects); Japan - epidemiology; Kidney Neoplasms - epidemiology; Kidney Neoplasms - metabolism; Kidney Neoplasms - pathology; Male; Mass Screening; Medical sciences; Mice; Mice, Nude; Neoplasm Staging; neuroblastoma; Neuroblastoma - epidemiology; Neuroblastoma - metabolism; Neuroblastoma - secondary; Neurology; PARP-1; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques; Phosphorylation; Poly (ADP-Ribose) Polymerase-1; Poly(ADP-ribose) Polymerases - analysis; Poly(ADP-ribose) Polymerases - metabolism; Proto-Oncogene Proteins c-akt - metabolism; Survival Rate; Tissue Array Analysis; Tumors of the nervous system. Phacomatoses; High; Nervous system diseases; Enzyme; Transferases; Glycosyltransferases; Akt protein kinase; Activation; Standard; AKT; mass screening; Malignant tumor; Neuroblastoma; Medical screening; PARP-1; Standards; NAD; Prevention; Anatomic pathology; Cell death; ADP-ribosyltransferase; Autonomic neuropathy; Pentosyltransferases; Cancer; Apoptosis
• ISSN: 0309-0167; 1365-2559
• DOI: 10.1111/j.1365-2559.2010.03522.x

Sartelet H, Ohta S, Barrette S, Rougemont A‐Laure, Brevet M, Regairaz M, Harvey I, Bernard C, Fabre M, Gaboury L, Oligny L L, Bosq J, Valteau‐Couanet D & Vassal G
(2010) Histopathology56, 607–616
High level of apoptosis and low AKT activation in mass screening as opposed to standard neuroblastoma
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.