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      Vascular endothelial growth factor and KIT expression in relation with microvascular density and tumor grade in supratentorial astrocytic tumors

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          Abstract

          PURPOSE: To evaluate the relationship between microvascular density and the expression of vascular endothelial growth factor (VEGF) and KIT as possible markers of angiogenic stimulus in astrocytic tumors and correlate it with histopathological grading. METHODS: We enrolled 99 surgical specimens of supratentorial astrocytic tumors for analysis of VEGF and KIT and subsequent correlation with MVD and grading. RESULTS: KIT and VEGF expression correlated with microvascular density (p<0.005) and both VEGF and microvascular density correlated with grading (p<0.005). KIT had no significant relationship with grading (p=0.657). CONCLUSION: KIT and VEGF constitute important pathways in the angiogenesis of astrocytomas and therefore are promising prognostic tools and options for therapeutic intervention.

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          Exciting new advances in neuro-oncology: the avenue to a cure for malignant glioma.

          Erwin G Van Meir, Costas Hadjipanayis, Andrew D. Norden … (2010)
          Malignant gliomas are the most common and deadly brain tumors. Nevertheless, survival for patients with glioblastoma, the most aggressive glioma, although individually variable, has improved from an average of 10 months to 14 months after diagnosis in the last 5 years due to improvements in the standard of care. Radiotherapy has been of key importance to the treatment of these lesions for decades, and the ability to focus the beam and tailor it to the irregular contours of brain tumors and minimize the dose to nearby critical structures with intensity-modulated or image-guided techniques has improved greatly. Temozolomide, an alkylating agent with simple oral administration and a favorable toxicity profile, is used in conjunction with and after radiotherapy. Newer surgical techniques, such as fluorescence-guided resection and neuroendoscopic approaches, have become important in the management of malignant gliomas. Furthermore, new discoveries are being made in basic and translational research, which are likely to improve this situation further in the next 10 years. These include agents that block 1 or more of the disordered tumor proliferation signaling pathways, and that overcome resistance to already existing treatments. Targeted therapies such as antiangiogenic therapy with antivascular endothelial growth factor antibodies (bevacizumab) are finding their way into clinical practice. Large-scale research efforts are ongoing to provide a comprehensive understanding of all the genetic alterations and gene expression changes underlying glioma formation. These have already refined the classification of glioblastoma into 4 distinct molecular entities that may lead to different treatment regimens. The role of cancer stem-like cells is another area of active investigation. There is definite hope that by 2020, new cocktails of drugs will be available to target the key molecular pathways involved in gliomas and reduce their mortality and morbidity, a positive development for patients, their families, and medical professionals alike.
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            Neuronal and glioma-derived stem cell factor induces angiogenesis within the brain.

            Lixin Sun, Ai-Min Hui, Qin Su … (2006)
            Stem cell factor (SCF) is overexpressed by neurons following brain injury as well as by glioma cells; however, its role in gliomagenesis remains unclear. Here, we demonstrate that SCF directly activates brain microvascular endothelial cells (ECs) in vitro and induces a potent angiogenic response in vivo. Primary human gliomas express SCF in a grade-dependent manner and induce normal neurons to express SCF in brain regions infiltrated by glioma cells, areas that colocalize with prominent angiogenesis. Downregulation of SCF inhibits tumor-mediated angiogenesis and glioma growth in vivo, whereas overexpression of SCF is associated with shorter survival in patients with malignant gliomas. Thus, the SCF/c-Kit pathway plays an important role in tumor- and normal host cell-induced angiogenesis within the brain.
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              Microvessel density is a prognostic indicator for patients with astroglial brain tumors.

              S Leon, R Folkerth, P M Black (1996)
              Microvessel density in tumors, a measure of angiogenesis, has been shown to be a prognostic indicator that correlates with an increased risk of metastasis in various epithelial cancers and with overall and relapse free survival in patients with breast cancer. Astrocytic brain tumors, particularly malignant astrocytomas, are recognized to be highly vascular tumors with potent angiogenic activity. However, the prognostic significance of microvessel density in these tumors is not known. Sections from formalin fixed paraffin embedded tumor tissue from 93 unselected adult patients with supratentorial astrocytic brain tumors were immunostained for factor VIII-related antigen in order to highlight microvessel endothelial cells. Microvessels were counted at 200x and 400x magnification. Microvessel density was graded as 1+ to 4+ on 1 low power field, without knowledge of clinical outcome. Microvessel count and microvessel grade were correlated with postoperative survival using the Cox proportional hazards regression model. The prognostic significance of microvessel count and grade were also compared with established prognostic indicators, including patient age, Karnofsky performance status, and tumor histology using multivariate analyses. Both microvessel grade and microvessel count correlated significantly with postoperative survival by univariate analysis in both previously untreated and treated patients. Patients with tumors containing a microvessel Grade of 3+ or 4+ had significantly shorter survival time than patients with a microvessel Grade of 1+ or 2+ (P = 0.0022). Likewise, patients with microvessel counts of 70 or greater had significantly shorter survival than those with microvessel counts of fewer than 70 (P = 0.041). Patient age, Karnofsky performance status, tumor histology, and extent of resection were also correlated with survival by univariate analysis. Microvessel count was further shown to be an independent prognostic indicator by multivariate analyses. There were correlations between microvessel density and patient age and between microvessel density and astrocytic tumor grade. These findings support the importance of microvessel density as a prognostic indicator of postoperative survival of patients with astroglial brain tumors. Regional tumor heterogeneity may limit the use of these techniques for routine pathologic examination.
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                Author and article information

                Contributors
                Thaís Heinke: Role: ND
                Kleber Simões do Espiríto Santo: Role: ND
                Adhemar Longatto Filho: Role: ND
                João Norberto Stavale: Role: ND
                Journal
                Journal ID (publisher): acb
                Title: Acta Cirurgica Brasileira
                Abbreviated Title: Acta Cir. Bras.
                Publisher: Sociedade Brasileira para o Desenvolvimento da Pesquisa em Cirurgia (São Paulo )
                ISSN: 1678-2674
                Publication date (Print): January 2013
                Volume: 28
                Issue: 1
                Pages: 48-54
                Affiliations
                [1 ] Universidade Federal de São Paulo Brazil
                [2 ] Hospital das Clínicas Luzia de Pinho Melo Brazil
                [3 ] Universidade de São Paulo Brazil
                Article
                Publisher ID: S0102-86502013000100008
                DOI: 10.1590/S0102-86502013000100008
                SO-VID: 07fb1587-4119-4d82-a9fa-def7293021f4
                License:

                http://creativecommons.org/licenses/by/4.0/

                History
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                SciELO Brazil

                Self URI (journal page): http://www.scielo.br/scielo.php?script=sci_serial&pid=0102-8650&lng=en
                Categories
                Subject: SURGERY

                ScienceOpen disciplines: Surgery
                Keywords: Immunohistochemistry,Glioma,Neovascularization, Pathologic
                Data availability:
                ScienceOpen disciplines: Surgery
                Keywords: Immunohistochemistry, Glioma, Neovascularization, Pathologic

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