AXIN1 Expression and Localization in Meningiomas and Association to Changes of APC and E-cadherin

Abstract

Background/aim: Tumor suppressor gene AXIN1 is an inhibitor of Wnt signaling pathway. It down-regulates the pathway's main signaling effector molecule, beta-catenin, in an AXIN-based destruction complex. In the present study we investigated the involvement of AXIN1 in intracranial meningioma.

Materials and methods: Loss of heterozygosity and microsatellite instability analyses were performed. The consequences of genetic changes on protein expression levels were studied in the same patients by immunohistochemistry.

Results: Allelic deletions of AXIN1 gene were found in 21.1% of meningiomas. Microsatellite instability was also observed in 5.3% of cases. Weak or lack of AXIN1 expression was found in 21.9% of meningiomas. We found strong statistical correlations between cytoplasmic localization of AXIN1 and its weak expression and also between the simultaneous cytoplasmic and nuclear localizations and moderate and strong expression levels (p<0.000). The findings on AXIN1 were compared to concomitant expression of APC, beta-catenin and E-cadherin in the same patients by Chi-Square tests and Pearson's correlations. Analysis revealed that AXIN1 genetic changes were significantly associated to lack of the expression of APC and presence of mutant APC proteins (p<0.018). Moderate and strong cytoplasmic and nuclear AXIN1 expressions were positively correlated to strong expression of E-cadherin (p<0.05).

Conclusion: Our findings on genetic changes and expression levels of AXIN1 bring novel data on its involvement in meningeal brain tumors and reveal AXIN1's relation to specific Wnt molecules.

Keywords: AXIN1; Wnt signaling; immunohistochemistry; loss of heterozygosity; meningiomas.