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Aim: The aim of our study was to evaluate the impact of tumor microenvironment (visual inflammation, inflammatory ICAM-1 expression) on the expression of vascular endothelial growth factor receptor 2 (VEGFR-2). Methods: Surgically excised GBM tissues (n = 42) were histologically examined for the overall extent of inflammation (score 1-3, based on typical appearance of inflammation, including presence of edema and inflammatory cell infiltration). After immunohistochemical staining procedure, tissue expression of ICAM-1 (optical density using pixel analysis software) as well as the number of VEGFR-2 positive (VEGFR-2+) blood vessels (per microscopic field) and endothelial staining intensity of VEGFR-2 (score 0-3) were determined. Results: In individual GBM samples, the extent of inflammation varied, being in the whole group 1.9 ± 0.7 (mean ± SD). Mean optical density of ICAM-1 (one of the mediators of inflammation) was 57,0 ± 27.1 (mean ± SD). The number of VEGFR-2+ blood vessels per microscopic field and endothelial VEGFR-2 staining intensity were 6.2 ± 2.4 (mean ± SD) and 1.2 ± 0.8 (mean ± SD) respectively. A positive association was found between VEGFR-2 staining intensity and the extent of inflammation (p = 0.005). Moreover, VEGFR-2 staining intensity correlated with the expression level of tissue ICAM-1 (p = 0.026). Conclusions: The expression of VEGFR-2 – one of the targets of anti-angiogenic therapy – depends on GBM microenvironment. Importantly, higher VEGFR-2 levels were seen in the presence of more pronounced inflammation, whereas in less inflamed tissues only weak expression of VEGFR-2 was found. Later has to be taken into consideration when VEGFR-2 targeting anti-angiogenetic drugs are tested in the treatment of GBM. This work was supported by grant IUT2-4. Disclosure: All authors have declared no conflicts of interest.

Aim: Glioblastoma multiforme (GBM) by its nature is radio-resistant because with postoperative radiotherapy only short-term stabilization of the disease can be achieved. Prior studies suggest that a higher level of DNA repair enzyme DNA-PK in GBM cells is one cause of the resistance. In current study we tried to identify factors that are associated with higher levels of DNA-PK in GBM. Somatostatin has been shown to be involved in many anti-tumor biological processes, such as inhibition of cell proliferation and the promotion of apoptosis. Therefore, we studied the expression of somatostatin receptor 1 (SSTR1) in GBM tissue and surrounding microenvironment. Methods: Surgically excised GBM tissues (n = 42) were immunohistochemically stained according to standard procedure. Staining intensity of DNA-PK was determined using an arbitrary score (0-3). For SSTR1, the proportion (%) of SSTR-positive (SSTR1+) tumor cells, the number of SSTR1+ blood vessels (per microscopic field) and endothelial SSTR1 staining intensity (score 0-3) were assessed. All individual parameters were characterized by the average value of 10 microscope fields. DNA-PK expression was correlated to SSTR1. Results: All markers were evaluated by two independent investigators whose results were in good accordance (R = 0.8, p Conclusions: The level of DNA repair enzyme DNA-PK in GMB tissue depends on SSTR1 expression in tumor and surrounding microenvironment. The potential of somatostatin in modulating DNA-PK levels and thereby cytotoxic treatment sensitivity has to be clarified in further studies. This work was supported by grant IUT2-4 and by Novartis Pharma unrestricted grant. Disclosure: All authors have declared no conflicts of interest.

Background Glioblastoma multiforme (GBM) is the most aggressive type of brain tumor in adults. Histologically, GBMs are highly angiogenic. It has been suggested that GBM stem cells might support tumor vascularization. The aim of our study was to evaluate the association between CD133-positive (CD133+) cancer stem cells and blood vessels in GBM tissue. Methods Between Jan 2006 and Dec 2008, 42 patients (30-77 years) received postoperative radiotherapy and chemotherapy. Surgically excised GBM tissues were examined for CD133 expression prior anticancer therapy. After immunohistochemistry, the proportion of CD133+ stem cells (%), the number of CD133+ blood vessels (per microscopic field), and the staining intensity of endothelial CD133 expression (arbitrary score 0-3) were evaluated. Results The expression of CD133 was determined by 2 independent researchers whose results were in good accordance. The proportion of CD133+ GBM stem cells was 33% ± 24% (mean ± SD). GBM tissue consisted of both CD133+ and CD133- blood vessels. However, endothelial staining of CD133 was found in all types of GBM blood vessels, including small capillaries and microvascular proliferations. The number of CD133+ blood vessels per microscopic field was 1.4 ± 1.3 (mean ± SD), and the endothelial CD133 staining intensity 1.0 ± 0.5 (mean ± SD). A significant association was found between the proportion of CD133+ stem cells and the number of CD133+ blood vessels (p = 0.004). Also, a correlation between the number of CD133+ blood vessels and the endothelial CD133 staining intensity was detected (p Conclusion In the present study, a significant association was found between CD133+ GBM stem cells and CD133+ blood vessels. Favourable CD133+ expression has to be taken into account in the strategies under preclinical or clinical development for GBM stem cell targeting. This work was supported by grant ETF8862 and Roche scientific grant. Disclosure J. Jaal: This work was partly supported by Roche scientific grant. M. Kase: This work was partly supported by Roche scientific grant. A. Minajeva: This work was partly supported by Roche scientific grant. K. Niinepuu: This work was partly supported by Roche scientific grant. S. Kase: This work was partly supported by Roche scientific grant. M. Vardja: This work was partly supported by Roche scientific grant. T. Asser: This work was partly supported by Roche scientific grant.