engleski

Genetic landscape of human intracranial meningioma

Intracranial meningiomas are considered as one of the most common primary brain tumors. Although most of them are considered benign (cca 80%) and classified as WHO grade I, remaining 20% classified as atypical (grade II) and anaplastic (grade III) show aggressive character and higher probability of recurrence. The malfunctioning of different vital cellular processes can lead to initiation and progression of tumors. In the present study we tried to identify changes in molecular effectors of different cellular events involved in tumorigenesis: mismatch repair system, activation of Wnt signalling pathway and epithelial to mesenchymal transition (EMT). EMT is triggered by the so called “cadherin switch” during which cells undergo molecular changes, become motile and metastasize. In order to describe genetic landscape and identify potential markers for the progression of meningioma, we investigated main actors of mismatch repair system (MMR) – MLH1 and MSH2, of Wnt signalling pathway – DVL3 and AXIN and of EMT – E-cadherin. Genetic changes of MLH1, MSH2, DVL3, AXIN and E-cadherin gene (CDH1) were analysed on 36 samples of meningioma with different grades of malignancy. Genetic alternations (loss of heterozygosity, microsatellite instability) were tested by PCR and Spreadex gel electrophoresis using microsatellite markers D3S1611 (MLH1), BAT26 (MSH2), D16S3399 (AXIN1), D3S1262 (DVL3), D16S3025 (CDH1). Furthermore, we tested if the expression of E- cadherin protein was influenced by its genetic alternations. To assess E- cadherin expression, we used DAB-labelled immunohistochemical reaction (EnVisionTM, Dako REALTM) and monoclonal antibody (monoclonal mouse anti-human E-cadherin (clone NCH-38, Dako North America, Inc.). Although genetic changes of CDH1 were observed in only 15% of samples, 53% of them showed extremely low cytoplasmic expression of E-cadherin. We also noted a positive correlation between genetic changes of CDH1 and AXIN1 (P=0, 028, ρ=0, 011). Our studies have shown that 64% of samples had at least one genetic alternation in one of investigated molecules. Most frequently changed was MLH1 gene in 36% of samples. Further studies on higher number of meningioma could confirm our findings and reveal potential biomarkers of meningioma progression.

intracranial meningioma ; Wnt signalling ; EMT

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