Department of Pathology, Kashan University of Medical Sciences, Kashan, Iran.
Anatomical Sciences Research Center, Basic Sciences Research Institute, Kashan University of Medical Sciences, Kashan, Iran.
Asian Pac J Cancer Prev. 2020 Oct 1;21(10):2889-2894. doi: 10.31557/APJCP.2020.21.10.2889.
Glioblastoma multiforme (GBM) is a grade IV glioma and accounts for 15% of all primary brain tumors. This GBM has a median survival range of less than 2 years after diagnosis and it is highly vascularized by neoformed vessels. Neoangiogenesis is a crucial factor in the malignant tumoral behavior and prognosis of patients and Nestin protein belongs to class VI which is expressed in endothelial cells of neoformed vessels in GBM. Our study shows the correlation between EGFR mutation and Nestin expression in endothelial of neoformed vessels in GBM.
We analyzed 40 GBM samples by immunohistochemistry staining. The immunohistochemical expression of EGFR in tumoral cells and Nestin in endothelial cells in paraffin sections were analyzed. EGFR scoring was the based on staining intensity. Score 0 shows No staining, Score1, mild to moderate staining and score2 sever staining. Microvascular density (MVD) was evaluated with Nestin-immunoreactive.
The mean of MVD was 14.6 ±8.25. Nestin-MVD was significantly higher in GBM with sever vascular prolifration (p-value=0.01). EGFR was expressed in 92.5% of samples. The EGFR scoring for tumoral tissue was 7.5%(score:0), 22.5% (score:1) and 70% (score:2). There was a significant relationship between EGFR expression and MVD (p-value=0.017).
We suggest that some important mutations as like as EGFR in GBM is responsible for inducing angiogenesis and vascular proliferation. Nestin overexpression as a novel marker might reflect the extent of neoangiogenesis, thus target therapy against EGFR pathway and anti angiogenic may be useful for GBM treatment.
多形性胶质母细胞瘤(GBM)是 4 级神经胶质瘤,占所有原发性脑肿瘤的 15%。这种 GBM 在诊断后中位生存时间不到 2 年,其血管新生由新生血管形成。新生血管生成是恶性肿瘤行为和患者预后的关键因素,巢蛋白属于 VI 类,在 GBM 的新生血管内皮细胞中表达。我们的研究表明,EGFR 突变与 GBM 新生血管内皮巢蛋白表达之间存在相关性。
我们通过免疫组织化学染色分析了 40 个 GBM 样本。分析了石蜡切片中肿瘤细胞中 EGFR 和内皮细胞中巢蛋白的免疫组织化学表达。EGFR 评分基于染色强度。评分 0 表示无染色,评分 1 表示轻度至中度染色,评分 2 表示重度染色。用巢蛋白免疫反应性评估微血管密度(MVD)。
MVD 的平均值为 14.6±8.25。在血管增殖严重的 GBM 中,巢蛋白-MVD 明显更高(p 值=0.01)。EGFR 在 92.5%的样本中表达。肿瘤组织的 EGFR 评分为 7.5%(评分:0)、22.5%(评分:1)和 70%(评分:2)。EGFR 表达与 MVD 之间存在显著关系(p 值=0.017)。
我们认为,像 GBM 中的 EGFR 这样的一些重要突变负责诱导血管生成和血管增殖。巢蛋白的过度表达作为一种新的标志物可能反映了新生血管的程度,因此针对 EGFR 通路的靶向治疗和抗血管生成可能对 GBM 的治疗有用。