The molecular pathology of p53 in primitive neuroectodermal tumours of the central nervous system

Abstract

One hundred and one pre-treatment primary central primitive neuroectodermal tumours were analysed for the expression of p53 protein by immunohistochemistry using the monoclonal antibody DO-7. The staining intensity was classified into four groups: strong, medium, weak and negative and strong staining intensity was associated with the poorest survival. DNA sequencing of the p53 gene was performed in 28 cases representing all four staining groups. Mutations were found in only three of the strong staining tumours suggesting that DNA mutations were not common events and that in the majority of the tumours with over-expressed p53, the protein was likely to be wild-type. Results of immunohistochemistry showed a significantly positive relationship between the expression of p53 and Bax and Bcl-2 proteins, but not Waf-1. Multivariate analyses supported the prognostic value of p53 immunostaining in central primitive neuroectodermal tumours and also of age and gender of patients.

Increased p53 immunopositivity in anaplastic medulloblastoma and supratentorial PNET is not caused by JC virus

“…While extracerebellar PNET were included in several earlier studies, p53 immunoreactivity was not reported separately for these lesions [14,15]. Ho and colleagues documented p53 mutations in 6 of 14 sPNET but did not examine protein expression [36].…”

P53 and Ki-67 expression in primary pediatric brain tumors: Does it correlate with presentation, histological grade, and outcome?

“…[ 4 5 ] Ki-67 and p53 expression was calculated as percentage positivity. [ 6 7 8 ] Patients were followed up after discharge with Glasgow outcome score (GOS) at three and 6 months (as possible). Good recovery was quantified by GOS (4 and 5), fair recovery by GOS (3), and poor recovery with GOS (1 and 2).…”

Aberrant over-expression of a forkhead family member, FOXO1A, in a brain tumor cell line

“…Although apparently paradoxical, high expression of bona fide tumor suppressor genes, including p16 [18] and p53 [19], have been reported in solid tumor specimens. In the latter study, high levels of wild type p53 were detected in CNS-PNETs.…”

“…However, our microarray expression analyses of CNS-PNET specimens revealed a surprisingly high level of FOXO1A expression in one CNS-PNET cell line relative to five other CNS-PNET cell lines and two normal fetal brain specimens. Although over expression of bona fide tumor suppressor genes such as p16 and p53 in cancer specimens has been reported [18,19] the molecular mechanisms by which this occurs and the biological significance of this phenomenon are poorly understood. Since FOXO1A is considered to be a tumor suppressor gene, and little is known about the regulation of FOXO1A mRNA expression levels in mammalian cells, we investigated the molecular mechanisms underlying the high expression of FOXO1A in the PER-453 CNS-PNET cell line.…”