Anaplastic astrocytoma and glioblastoma are malignant brain tumors with a poor prognosis. The aim of our study was the complex investigation of the factors, those influence their aggressive behavior and proliferation (Ki-67, EGFR, MMP-9, PR, р53, vascular network formation), and the evaluation of their prognostic impact. These data could be used for optimization of target therapy in different groups of patients with diffuse astrocytic tumors Grade III-IV. Our study included 30 patients who were put through brain surgery for the first time and were divided into two equal groups: 15 patients who experienced a recurrence within 1 year after the surgery (1st group) and 15 patients without recurrence within 1 year after the surgery (2nd group). Postoperative tumor materials were obtained in formalin-fixed, paraffin-embedded blocks. In addition, we investigated the case histories of these patients. The expression of Ki-67, EGFR, MMP-9, PR, р53, VEGF, and CD34 was evaluated with immunohistochemical testing. Chi-squared test, Mann-Whitney U and Kruskal-Wallis H tests were performed for comparison of quantitative parameters between groups. Spearman’s rank correlation coefficient was used for the measure of rank correlation between quantitative variables. Results of our study showed, that there was a tendency (Uemp=75,00; р>0.05) to higher proliferative index in the 1st group (18,29±3,44) compared to the 2nd group (16,57±3,09). EGFR expression was significantly higher in the 1st group (Uemp=70.50; p<0.05). Moreover, the higher EGFR expression was associated with higher MMP-9 expression (Uemp=7.500; p<0.01) and lower p53 expression (rs= –0.62, p<0.001). The higher MMP-9 expression was also associated with higher vascularization index (MVD(VEGF)/MVD(CD34)) (rs=0.43; p<0.05). Our data confirm the close connections of different factors of tumor aggressiveness and the presence of molecule-biological discrepancy in homogenous histologically, but heterogenous prognostically groups of tumors. This evidence may be used in future for better-personalized therapy of patients with diffuse astrocytic tumors Grade III-IV.