Netto Gabriel Corteze, Bleil Cristina Birlem, Hilbig Arlete, Coutinho Lígia Maria Barbosa
Post-graduate Program in Pathology, Fundação Faculdade Federal de Ciências Médicas de Porto Alegre (FFFCMPA), Rio Grande do Sul, Brazil.
Neuropathology. 2008 Feb;28(1):17-23. doi: 10.1111/j.1440-1789.2007.00825.x.
Angiogenesis has been proposed as essential for the growth of solid tumors. The determinants of this process, the growth factors and the vascular endothelial receptors have brought a potential in the tumor prognostic determination as well as perspectives of "targets" for antiangiogenic therapy. In oligodendrogliomas (OL), angiogenesis is little known and/or has generated conflicting results. In order to clarify angiogenesis in OL, we have evaluated the immunohistochemical expression of vascular endothelial growth factor (VEGF) and the microvascular density (MVD) through the expression of TGF-beta (CD105/endoglin) (MVD-CD105) and CD34 (MVD-CD34) receptors using the Chalkley point method in 30 OL. No significant immune reaction was found for the VEGF. There was expression in <10% of tumor cells and/or staining of weak intensity in 15 (50.0%), >10% of cells and moderate intensity staining in 1 (3.33%), and negative expression in 14 (46.67%). If present, the expression was restricted to tumor and endothelial cells. Our findings suggest that VEGF has little influence on OL angiogenesis. All specimens showed CD105 and CD34 expression in the intratumor vascular endothelium, suggesting involvement of CD105 in OL angiogenesis. The mean +/- SD MVD-CD105 and MVD-CD34 were 10.83 +/- 2.24 and 11.00 +/- 2.76 in OL (P = 0.086; r = 0.319); 10.00 +/- 2.00 and 10.40 +/- 3.02 in OL grade II (n = 15) (P = 0.547; r = 0.105), and 11.67 +/- 2.22 and 11.53 +/- 2.45 in OL grade III (n = 15) (P = 0.817; r = 0.551), respectively. The absence of correlation between DMV-CD105, DMV-CD34 and tumor grades suggests that anti-CD105 and anti-CD34 antibodies have different vascular specificities. MVD-CD105 was greater in OL grade III than in OL grade II (P = 0.0032), indicating an increase in the vascular neoformation, something which must be evaluated as a possible prognostic factor in OL. Both TGF-beta and CD105 bring perspectives as "targets" for antiangiogenic treatments in OL.
血管生成被认为是实体瘤生长所必需的。这一过程的决定因素,即生长因子和血管内皮受体,为肿瘤预后判定带来了潜力,也为抗血管生成治疗提供了“靶点”。在少突胶质细胞瘤(OL)中,血管生成鲜为人知,且/或产生了相互矛盾的结果。为了阐明OL中的血管生成,我们通过使用Chalkley点计数法,在30例OL中评估了血管内皮生长因子(VEGF)的免疫组化表达以及通过转化生长因子β(CD105/内皮糖蛋白)(MVD - CD105)和CD34(MVD - CD34)受体的表达来评估微血管密度(MVD)。未发现VEGF有明显的免疫反应。在15例(50.0%)肿瘤细胞中,VEGF表达<10%且/或染色强度较弱;1例(3.33%)肿瘤细胞中,VEGF表达>10%且染色强度中等;14例(46.67%)肿瘤细胞中,VEGF呈阴性表达。若有表达,其表达仅限于肿瘤细胞和内皮细胞。我们的研究结果表明,VEGF对OL血管生成影响较小。所有标本的肿瘤内血管内皮均显示CD105和CD34表达,提示CD105参与了OL血管生成。OL中MVD - CD105和MVD - CD34的平均值±标准差分别为10.83±2.24和11.00±2.76(P = 0.086;r = 0.319);II级OL(n = 15)中分别为10.00±2.00和10.40±3.02(P = 0.547;r = 0.105),III级OL(n = 15)中分别为11.67±2.22和11.53±2.45(P = 0.817;r = 0.551)。DMV - CD105、DMV - CD34与肿瘤分级之间缺乏相关性,提示抗CD105和抗CD34抗体具有不同的血管特异性。III级OL中的MVD - CD105高于II级OL(P = 0.0032),表明血管新生增加,这一点必须作为OL可能的预后因素进行评估。转化生长因子β和CD105都为OL抗血管生成治疗提供了“靶点”。