Meningiomas exhibit loss of heterozygosity of the APC gene

Pećina‐Šlaus, Nives; Martić, Tamara Nikuševa; Tomas, Davor; Beroš, Vili; Zeljko, Martina; Čupić, Hrvoje

doi:10.1007/s11060-007-9500-6

Cited by 24 publications

(13 citation statements)

References 24 publications

(20 reference statements)

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“…The results obtained on medulloblastoma are in accordance with the reported data [16][17][18][19]. Our previous results demonstrated that other Wnt molecular components were also changed in CNS tumors [20][21][22].…”

Section: Discussionsupporting

confidence: 91%

Changes of AXIN-1 and Beta-Catenin in Neuroepithelial Brain Tumors

Martić

Pećina‐Šlaus

Kušec

et al. 2009

Pathol. Oncol. Res.

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In the present study changes of components of Wnt signaling pathway--axin (AXIN1) and beta-catenin (CTNNB1) in a sample of 72 neuroepithelial brain tumors were investigated. AXIN-1 gene was tested by PCR/loss of heterozygosity (LOH). Immunostaining and image analysis revealed the quantity and localization of relevant proteins. Polymorphic marker for AXIN-1, showed LOH in 11.1% of tumors. LOH was distributed to 6.3% of glioblastomas, one was found in neuroepithelial dysembrioplastic tumor and one in medulloblastoma. Down regulation of axin expression and up regulation of beta-catenin were detected in the analyzed tumors. Axin was observed in the cytoplasm in 68.8% of samples, in 28.1% in both the cytoplasm and nucleus and 3.1% had no expression. Beta-catenin was observed mainly in the nucleus and cytoplasm (59.4%). Expression in 34.4% of samples was in the cytoplasm and 6.3% showed no expression. Comparison of mean values of relative increase of axin and beta-catenin showed that they are significantly reversely proportional (P = 0.014). Relative quantity of beta-catenin in patients with gross deletion of AXIN1 was significantly higher in comparison to patients without LOH (P = 0.040). Our results demonstrate that changes of key components of the Wnt signaling play a role in neuroepithelial brain tumors.

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Section: Discussionsupporting

confidence: 91%

Changes of AXIN-1 and Beta-Catenin in Neuroepithelial Brain Tumors

Martić

Pećina‐Šlaus

Kušec

et al. 2009

Pathol. Oncol. Res.

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“…; Pećina‐Šlaus et al . ). However, potentially responsible signalling pathways, and the molecular aetiology and pathogenesis of this tumour still remains to be elucidated.…”

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confidence: 97%

“…Loss of merlin, protein encoded by NF2, is a consistent finding in all neurofibromatosis type 2-associated meningiomas and in about half of sporadic benign cases (Lee et al 2004;Fuller & Perry 2005; Pe cina-Slaus 2013). Relevant genetic alterations in atypical and anaplastic meningiomas, as well as in specific histological subtypes, have not as yet been fully defined, although several molecular studies have examined alterations in many tumour suppressor genes and oncogenes (Weber et al 1997;Wrobel et al 2005;Brunner et al 2006;Pe cina-Slaus et al 2008). However, potentially responsible signalling pathways, and the molecular aetiology and pathogenesis of this tumour still remains to be elucidated.…”

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confidence: 99%

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

Pećina‐Šlaus

Kafka

Vladušić

et al. 2016

Int J Experimental Path

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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.

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“…Since misregulation of signaling pathways relies on intrinsic molecular dependancies, we decided to investigate how data obtained on AXIN1 in the present experimental work relate to our previous findings on meningiomas regarding APC, Ecadherin and beta-catenin (26,27). Therefore, we correlated all the assesed variables anew.…”

Section: Resultsmentioning

confidence: 91%