P53 Protein Overexpression Identifies a Group of Central Primitive Neuroectodermal Tumors with Poor Prognosis
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Lookup NU author(s): Dr Evelyn Jaros, Professor John LunecORCiD, Emeritus Professor Robert Perry, Professor Andrew Pearson
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Primitive neuroectodermal tumours (PNET's) or medulloblastomas are common primary brain tumours of childhood. Current treatment protocols achieve 50-60% cures. However, it has proved difficult to develop better treatment for the remaining patients because prognostic factors are not established. We have investigated the prognostic value of p53 protein expression in 87 PNET's using immunohistochemistry with DO-7 and CM-1 antibodies on biopsy paraffin sections. Eight patients (9%) had intensely reactive tumour cell nuclei, and a significantly reduced survival (P = 0.002); only one survives and this with a recurrent tumour 50 months following diagnosis. Sixty eight per cent of patients had faintly reactive tumour cell nuclei, a reduced survival up to 4 years but a long term survival not significantly different (P = 0.41) from 23% of patients with p53 negative PNET's; the 10 year survival rates were 37% and 40%, respectively. Males had a reduced survival (P = 0.04) with a 2-fold relative risk of death compared to females. Multivariate analysis showed that intense overexpression of p53 protein identifies a group of PNET patients with a 7-fold relative risk of death compared to all other cases, irrespective of sex. This marked difference suggests the involvement of p53 in the pathogenesis of PNET's which have a particularly poor response to treatment, and should help to develop new therapies for this group of patients.
Author(s): Jaros, E., Lunec, J., Perry, R.H., Kelly, P.J., Pearson, A.D.J.
Publication type: Article
Publication status: Unknown
Journal: British Journal of Cancer
Year: 1993
Volume: 68
Issue: 4
Pages: 801-807
Print publication date: 01/10/1993
ISSN (print): 0007-0920
ISSN (electronic): 1532-1827