engleski

Loss of p53 expression is accompanied with upregulation of beta-catenin in meningiomas: a concomitant reciprocal expression

A crosstalk between Wnt and p53 signalling pathways in cancer has long been suggested. We investigated the involvement of these pathways in meningioma by analysing their main effector molecules, beta- catenin and p53. Cellular expression of p53 and beta-catenin proteins and genetic changes in TP53 in 59 meningiomas were analysed by immunohistochemistry, PCR/RFLP and direct sequencing of TP53 exon 4. All findings were analysed with statistical analysis. Our analyses showed that 47.5% of the total sample demonstrated the loss of expression of p53 protein. Moderate and strong p53 expressions in the nucleus were observed, respectively, in 8.5% and 6.8% of meningiomas. Gross deletion of TP53 gene was observed in one meningioma (9% of samples), but nucleotide alterations were observed in 35.7% of meningiomas. Contrary, 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 bring novel reports on p53 involvement in meningeal brain tumours and reveal the complex relationship between Wnt and p53 signalling, suggesting an important role of beta-catenin.

beta-catenin ; meningioma ; p53 ; protein expression ; Wnt and p53 signalling

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