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Loss of p53 expression is accompanied by upregulation of beta‐catenin in meningiomas: a concomitant reciprocal expression
Author(s) -
PećinaŠlaus Nives,
Kafka Anja,
Vladušić Tomislav,
Tomas Davor,
Logara Monika,
Skoko Josip,
Hrašćan Reno
Publication year - 2016
Publication title -
international journal of experimental pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.671
H-Index - 72
eISSN - 1365-2613
pISSN - 0959-9673
DOI - 10.1111/iep.12186
Subject(s) - downregulation and upregulation , wnt signaling pathway , meningioma , immunohistochemistry , biology , cancer research , catenin , beta catenin , carcinogenesis , signal transduction , gene , pathology , medicine , microbiology and biotechnology , genetics , immunology
Summary 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 TP 53 were analysed by immunohistochemistry, PCR / RFLP and direct sequencing of TP 53 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 TP 53 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.