Estudo imuno-histoquímico e molecular de gliomas

Abstract

Gliomas are the most common primary brain tumor, accounting for over 70% of all primary CNS neoplasms. They are histologically heterogeneous tumors and classified by the World Health Organization to varying degrees, according to their cellular characteristics and its invasiveness. The astrocytomas, oligodendrogliomas and ependymal cell tumors represent the types of gliomas. In gliomas, changes occur in different signaling pathways and from the knowledge of such changes it may be established ways of diagnosis of these tumors; and a better prognosisi can be made. Moreover, these signaling pathways are important as potential therapeutic targets. The molecular alterations present in various types and subtypes of gliomas may be different, and it is important for the understanding of the disease and may be useful for diagnosis. Thus, we studied in this work, molecular and immunohistochemical methods, the frequency of polymorphisms and mutations in PTEN, KRAS, BRAF, IDH1 and IDH2 and the expression of PTEN, BRAF, TGF-β and Ki-67 in association with clinical features of 38 patients with glioma. In sequence analysis, we detected a silent mutation in PTEN in a patient with glioblastoma multiforme, and the R132H mutation in IDH1 in a patient with low-grade astrocytoma. In the remaining genes, we did not detect mutations or polymorphisms. We found a significant difference between the highest Ki-67 expression in high grade tumors compared to low grade tumors, as well as overexpression in BRAF II and grade IV gliomas, when compared to the I grade gliomas In expression analysis TGF-β II receptor, increased expression of the protein observed in the glioma compared to normal tissues. Both TβRII as in PTEN, we found no correlation between the expression and the stages of gliomas. Our data demonstrate that gliomas have superexpression of BRAF, regardless of the presence of BRAFV600E mutation. The change in expression between grades may be associated with malignant progression of these tumors. Gliomas have increased expression of TβRII, irrespective of the histological grade of the tumors, suggesting a role for TGF-β pathway in the pathogenesis of gliomas. The association of PTEN expression and gliomas can not be demonstrated. We did not detect changes in the KRAS and BRAF genes, but we can not rule out the importance of these genes in the formation of gliomas. Studies with larger numbers of samples of gliomas with the same tumor stages are needed to assess the influence of PTEN, KRAS and BRAF in the formation and progression of gliomas.