Institute of Neurosurgery, Università Cattolica del Sacro Cuore, Rome, Italy.
Institute of Human Anatomy, Università Cattolica del Sacro Cuore, Rome, Italy.
Mod Pathol. 2018 Sep;31(9):1361-1366. doi: 10.1038/s41379-018-0046-2. Epub 2018 Apr 30.
We hypothesized that in glioblastoma recurring after radiotherapy, a condition whereby the brain endothelium undergoes radiation-induced senescence, tumor cells with endothelial phenotype may be relevant for tumor neovascularization. Matched glioblastoma samples obtained at primary surgery and at surgery for tumor recurrence after radiotherapy, all expressing epidermal growth factor receptor variant III (EGFRvIII), were assessed by a technique that combines fluorescent in situ hybridization (FISH) for the EGFR/CEP7 chromosomal probe with immunostaining for endothelial cells (CD31) and activated pericytes (α Smooth Muscle Actin). Five EGFRvIII-expressing paired primary/recurrent glioblastoma samples, in which the tumor cells showed EGFR/CEP7 amplification, were then assessed by CD31 and α Smooth Muscle Actin immunofluorescence. In glomeruloid bodies, the ratio between CD31+ cells with amplified EGFR/CEP7 signal and the total CD31+ cells was 0.23 ± 0.09 (mean ± sem) and 0.63 ± 0.07 in primary tumors and in recurrent ones, respectively (p < 0.002, Student-t test). In capillaries, the ratio of CD31+ cells with amplified EGFR/CEP7 over the total CD31+ cells lining the capillary lumen was 0.21 ± 0.06 (mean ± sem) and 0.42 ± 0.07 at primary surgery and at recurrence, respectively (p < 0.005, Student-t test). Expression of α Smooth Muscle Actin by cells with EGFR/CEP7 amplification was not observed. Then, in glioblastoma recurring after radiotherapy, where the brain endothelium suffers from radiation-induced cell senescence, tumor-derived endothelium plays a role in neo-vascularization.
我们假设，在放疗后复发的胶质母细胞瘤中，由于脑内皮细胞经历了辐射诱导的衰老，具有内皮表型的肿瘤细胞可能与肿瘤新生血管形成有关。通过一种将表皮生长因子受体变体 III（EGFRvIII）的荧光原位杂交（FISH）与内皮细胞（CD31）和激活的周细胞（α平滑肌肌动蛋白）免疫染色相结合的技术，评估了在原发性手术和放疗后肿瘤复发时获得的匹配的 EGFRvIII 表达的胶质母细胞瘤样本。然后，通过 CD31 和 α 平滑肌肌动蛋白免疫荧光评估了 5 个 EGFRvIII 表达的配对原发性/复发性胶质母细胞瘤样本，其中肿瘤细胞显示 EGFR/CEP7 扩增。在肾小球样体中，具有扩增的 EGFR/CEP7 信号的 CD31+细胞与总 CD31+细胞的比例分别为 0.23±0.09（平均值±SEM）和 0.63±0.07，在原发性肿瘤和复发性肿瘤中分别为 0.23±0.09（p<0.002，Student-t 检验）。在毛细血管中，具有扩增的 EGFR/CEP7 的 CD31+细胞与沿毛细血管腔衬里的总 CD31+细胞的比例分别为 0.21±0.06（平均值±SEM）和 0.42±0.07，在原发性手术和复发时分别为 0.21±0.06（p<0.005，Student-t 检验）。具有 EGFR/CEP7 扩增的细胞中未观察到 α 平滑肌肌动蛋白的表达。然后，在放疗后复发的胶质母细胞瘤中，脑内皮细胞遭受辐射诱导的细胞衰老，肿瘤衍生的内皮细胞在新血管形成中起作用。
