engleski

Meningiomas: role of genetic instabilities of the E-cadherin gene

The numerous reports by many authors as well as our own results indicate that E-cadheirn plays a role in CNS tumors - meningiomas. The suppression of E-cadherin expression is regarded as one of the main molecular events responsible for dysfunction in cell-cell adhesion. It is now apparent that downregulation of E-cadherin expression is involved in meningioma development. Our studies on meningiomas of different grades showed that 73% of meningiomas had downregulation of E-cadherin expression. Intense downregulation was noticed in tumors with grades II and III. Our analysis on the genetic level of E-cadherin changes showed loss of heterozygosity (LOH) in 32% meningiomas investigated. Also, another type of genomic instability was detected in 11% of our sample ¾ MSI phenotype. The instability is the result of impaired cellular mismatch repair. Beta-catenin is the main effector molecule in wnt signaling and is bound to E-cadherin in adherens junctions. Beta-catenin was progressively upregulated from meningothelial to atypical, while 60% of anaplastic showed upregulation and nuclear localization of the protein. A significant association between the genetic changes of CDH1 and the nuclear localization of beta-catenin protein (P<0.022) was established in our study. Better understanding of meningioma genetic profile will elucidate pathophysiological mechanisms of tumor formation, and eventually offer improved prognostic markers for meningioma.

E-cadherin, meningioma

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