Loss of p53 expression is accompanied by upregulation of beta‐catenin in meningiomas: a concomitant reciprocal expression

Abstract

Crosstalk between Wnt and p53 signalling pathways in cancer has long been suggested. Therefore in this study we have investigated the involvement of these pathways in meningiomas by analysing their main effector molecules, beta-catenin and p53. Cellular expression of p53 and beta-catenin proteins and genetic changes in TP53 were analysed by immunohistochemistry, PCR/RFLP and direct sequencing of TP53 exon 4. All the findings were analysed statistically. Our analysis showed that 47.5% of the 59 meningiomas demonstrated loss of expression of p53 protein. Moderate and strong p53 expression in the nuclei was observed in 8.5% and 6.8% of meningiomas respectively. Gross deletion of TP53 gene was observed in one meningioma, but nucleotide alterations were observed in 35.7% of meningiomas. In contrast, beta-catenin, the main Wnt signalling molecule, was upregulated in 71.2%, while strong expression was observed in 28.8% of meningiomas. The concomitant expressions of p53 and beta-catenin were investigated in the same patients. In the analysed meningiomas, the levels of the two proteins were significantly negatively correlated (P = 0.002). This indicates that meningiomas with lost p53 upregulate beta-catenin and activate Wnt signalling. Besides showing the reciprocal relationship between proteins, we also showed that the expression of p53 was significantly (P = 0.021) associated with higher meningioma grades (II and III), while beta-catenin upregulation was not associated with malignancy grades. Additionally, women exhibited significantly higher values of p53 loss when compared to males (P = 0.005). Our findings provide novel information about p53 involvement in meningeal brain tumours and reveal the complex relationship between Wnt and p53 signalling, they suggest an important role for beta-catenin in these tumours.

Recurrence/Regrowth in Grade I Meningioma: How to Predict?

“…One study reported that p53 expression was associated with higher histological grades (II and III) and that the mutated p53 protein showed higher expression in older patients compared with youths (103). This finding is similar to the results of a study by our group, which observed immunostaining for mutated p53 in 90.6% of grade I meningiomas.…”

Genetic changes of MLH1 and MSH2 genes could explain constant findings on microsatellite instability in intracranial meningioma

“…Several new studies show that Wnt pathway plays important roles in meningioma. 8,[51][52][53][54][55][56] These studies concentrated on mutational analyses, proteomics, and so on, but did not search for MSI of Wnt signaling genes. In our previous work, we came across MSI for AXIN1 and CDH1 that in our opinion could not be neglected 57 and decided to explore this line of evidence on a larger group of meningiomas.…”

Molecular Genetics of Intracranial Meningiomas with Emphasis on Canonical Wnt Signalling

“…Recently a concomitant expression of beta-catenin and p53 was investigated [ 63 ]. The involvement of two signalling pathways in meningioma was questioned and analysed by their main effector molecules; beta-catenin for Wnt signalling and p53 for p53 signalling.…”