engleski

Genetic and protein changes of E-cadherin in meningiomas

The molecular mechanisms and candidate genes involved in development of meningiomas still need investigation and elucidation. In the present study thirty-three meningiomas were analyzed regarding genetic changes of tumor suppressor gene E-cadherin (CDH1), a component of adherens junction and an indirect modulator of the wnt signaling. Gene instability was tested by polymerase chain reaction/loss of heterozygosity (LOH) method. Protein expression was analyzed by immunohistochemistry. The results of our analysis showed altogether 32% of samples with LOH of the CDH1 gene. Interestingly, another type of genomic instability was detected &#190; ; replication error-positive samples (RER+). Three out of 28 heterozygous samples were RER-positive (11%). The instability is the result of impaired cellular mismatch repair. Fibrous and angiomatous cases showed higher percent of genetic changes, 67% and 75%, respecitively. Immunostaining showed that 58% of samples had downregulation of E-cadherin expression. Five out of nine samples with LOH were accompanied with the downregulation of E-cadherin protein expression (56%). One RER+ sample had lower expression of E-cadherin. We noticed that 37% of samples with lower E-cadherin expression had beta-catenin located in the nucleus. Also, 75% of samples with genomic instabilities had beta-catenin in the nucleus. Our findings demonstrated that there is significant association between the genetic changes of CDH1 and the nuclear localization of beta-catenin protein (c2 =5, 25, df =1, P<0, 022). Our results suggest that genetic instabilities of the E-cadherin gene have a role in meningioma development and progression. Detected microsatellite instability indicates that mismatch repair may also be targeted in meningioma.

CDH1; E-cadherin; immunostaining; loss of heterozygosity; meningiomas; replication error

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