engleski

Molecular alterations of E-cadherin and beta-catenin in brain tumor metastases

In the present study 47 brain metastases were analyzed regarding changes of E-cadherin (CDH1) and beta-catenin (CTNNB1). Gene instability was tested by PCR/loss of heterozygosity (LOH) method using three polymorphic regions linked to the CDH1 gene. Heteroduplex method was used to investigate mutations in beta-catenin. Proteins were analyzed by immunohistochemistry. The results of our analysis showed 42.2% of brain metastases with LOH of the CDH1 gene. The highest frequency of LOHs was observed in the metastases originating from primary sites with the diagnosis of lung adenocarcinoma and small cell lung cancer, with 83.3% and 75% of changes. In comparison to other lung cancer pathologies, those diagnoses were significantly associated to CDH1 changes with P=0.001. Metastases from breast and colon demonstrated changes in 55.6% and 50% of cases. Microsatellite instability was detected in 8.9% of cases. The mutational hot-spot of beta-catenin was not targeted. Downregulation of E-cadherin expression was observed in 83% of samples. Nuclear localization of beta-catenin was observed in 27.7% of metastases. Only 21.1% of samples with E-cadherin LOH had beta-catenin located in the nucleus. Image analysis showed that the quantities of proteins were significantly positively correlated (P = 0.008). Changes of E-cadherin and beta-catenin were present in brain metastases that we investigated. Lack of mutations of beta-catenin, the fact that it was not frequently found in the nucleus and the positive correlation between the two proteins quantities may suggest that the break-up of adherens junctions, and not the activation of wnt signaling, is responsible for metastasis formation.

E-cadherin (CDH1); beta-catenin (CTNNB1); brain metastasis; loss of heterozygosity; image analysis; immunostaining

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