engleski

Genetic and protein changes of AXIN1 and beta-catenin in neuroepithelial brain tumors

Neuroepithelial brain tumors are central nervous system neoplasms that embody a series of primary brain tumors including astrocytic, ependymal, choroid plexus, pineal pa¬ renchymal, and embryonal tumors. Tumors of neuroepithelial origin represent a heterogeneous group of intracranial neo¬ plasms with distinct features that control their ontogeny, pattern of invasion, clinical outcome, and prognosis. These features may reflect the complexity of the molecular and genetic alterations in pathways involved in the maintenance and progression of CNS tumors. It has been well documented that wnt genes, together with other components of wnt signaling pathway, are implicated in tumorigenesis. In the present study changes of components of wnt signaling pathway, axin (AXIN1) and β -catenin (CTNNB1) were investigated in neuroepithelial brain tumors in order to elucidate the genetic background ot this tumors. 72 neuroepithelial tumors were analyzed in this study regarding genetic changes of two genes: axin and β -catenin. LOH of the AXIN1 gene was detected by PCR amplification of the dinucleotid polymorphism (D16S521). The same samples were also analysed by immunohistochemistry for both axin and β -catenin proteins and evaluated by image analysis as staining density. PCR amplification of polymorphic marker for AXIN1 gene, showed LOH in 11.1% of total informative tumors. LOH was distributed to 6.3% of glioblastomas, one was found in neuroepithelial dysembrioplastic tumor and one in medulloblastoma. Immunostaining and Image analysis revealed the quantity and localization of relevant proteins. 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. β -catenin was observed mainly in the nucleus and cytoplasm (59, 4%). In 34, 4% it was localized in cytoplasm and 6, 3% of our sample had no expression. Comparison of mean values of relative increase of axin and β -catenin showed that they are significantly reversely proportional (P=0, 014). Relative quantity of β -catenin in patients with gross deletion of AXIN1 was significantly higher in comparison to patients without LOH (P=0, 040). In conclusion we believe that wnt signaling has important role in neuroepithelial brain tumor development. Our novel findings on changes of the wnt molecular components may contribute to better understanding of human brain tumors genetic profiles and also indicates for the first time the relation of quantities of those proteins.

axin; beta-catenin; neuroepithelial brain tumors; loss of heterozygosity; Image analysis

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