The aim of our study was to clarify the expression and gene copy number levels of protein phosphatase 1D magnesium-dependent, delta isoform (PPM1D), which is thought to be a regulator of the p53 protein in meningiomas of all three different WHO grades.
The objective of the following study is to grade meningiomas according to World Health Organization (WHO) 2007 criteria and to correlate the grade with degree of expression of epidermal growth factor receptor (EGFR) and p53.
However, the simultaneous RNAi-mediated targeting of uPAR and cathepsin B (pUC), in combination with irradiation, has greater potential application for the treatment of human meningioma in comparison to pU2 by decreasing p53 expression both in vitro and in vivo.
Our data suggests a role for the p53 pathway in the progression of meningiomas in which NF2 is inactivated, and highlights the importance of accounting for NF2 LOH in future studies of meningiomas and the p53 pathway.
We conclude that the Ki-67 and p53 labeling indices are useful additional tools in discriminating atypical from benign or anaplastic meningiomas, especially in histological borderline cases.
Six hundred and eighty glioma cases (298 glioblastoma (GBM)), 503 meningioma cases, and 1555 controls recruited in the Nordic-UK Interphone study, were analysed in association with three polymorphisms in p53 (rs2287499, rs1042533, rs1625895) and five polymorphisms in ATM ( rs228599, rs3092992, rs664143, rs170548, rs3092993).
In addition, the percentage of Ser 392 phosphorylated form of p53 protein was lower in meningiomas and other brain tumor types irrespective of tumor grade.
Only one single mutation was detected in a benign meningioma, confirming that p53 over-expression in meningiomas is commonly found in the absence of gene mutations, and that despite the significantly higher incidence of meningiomas in some Asian populations, this is not associated with a significantly higher rate of p53 mutations.
Therefore, we investigated if polymorphisms of p53 were associated with an increased risk of meningioma and glioma and integrated the polymorphism analyses with detailed information on family history of cancer.
In absence of p53 gene mutation, the high percentage of p14(ARF) gene methylation in high-grade meningioma may have been responsible for accumulation of wild-type p53 protein.
Previous mutational analysis of TP73, a structurally and functionally TP53 homologous gene located at 1p36.33, failed to demonstrate a significant rate of sequence variations linked to gene inactivation in meningiomas with 1p loss.
The present findings indicate that the loss of chromosome 22 may be involved with tumorogenesis of typical and aggressive meningiomas, while p53 gene deletions may be involved with malignant progression and recurrence in the aggressive meningiomas.
No mutations in p73 were identified in meningiomas. p73 RNA level was higher in more advanced tumors, but there was no correlation between the expression level of p73 and p21, a known p53 target gene.
PCR-SSCP method was performed in positive p53 protein immunoreactivity cases. p53 gene mutation rate was higher in the atypical (62.5%) and malignant (25%) meningiomas than in the benign meningioma (0%) (p=0.232).
No p53 positive cells were recognized in atypical meningiomas, and several cells were weakly stained in only two of 52 benign meningiomas. p53 staining index and immunoblot analysis indicated increasing amounts of p53 protein associated with subsequent recurrences of anaplastic meningiomas.
We examined the expression of the p53 and bcl-2 family in embolized meningiomas and investigated the interaction between them. p53 and its downstream effector p21 accumulated mainly in perinecrotic areas, where apoptosis was also observed. bcl-2 was often expressed in the areas distant from necrosis, whereas Bax was immunostained more intensely in the perinecrotic areas.
The data obtained from these studies suggest that elevated expression of the p53 or mdm2 protein products does not represent a common event in the development of human meningiomas.
Single-strand conformational polymorphism analysis of all three exons of CDKN2/p16 and exons 5-8 of p53 revealed no mutations in either HPCs or meningiomas.
Our results indicate that TP53 gene mutation may be considered as a marker for malignant transformation in meningioma. p53 immunoreactivity, even in the absence of detectable gene mutation, is also associated with atypia and does not appear in regular benign meningiomas.
The accumulation of wild-type p53 in a proportion of meningiomas may reflect this gene's role in DNA repair, or its enhanced stability when bound to cellular proteins such as the mdm-2 gene product.