Department of Neurosurgery, Medical and Dental University, Tokyo, Japan.
J Neurosurg. 2010 Aug;113(2):310-8. doi: 10.3171/2010.2.JNS091607.
Recent evidence suggests that a glioma stem cell subpopulation might contribute to radioresistance in malignant gliomas. To investigate this hypothesis, the authors examined recurrent malignant gliomas for histopathological changes after high-dose irradiation with Gamma Knife surgery (GKS) and external beam radiation therapy (EBRT).
Thirty-two patients with malignant gliomas (Grade 3 in 8 patients, Grade 4 in 24) underwent GKS in combination with EBRT. Serial MR and L-[methyl-(11)C] methionine PET images were employed to assess remnant or recurrent tumors after GKS. Twelve patients underwent surgical removal after GKS and EBRT. Histological sections were subjected to immunohistochemistry for MIB-1, factor VIII, and stem cell markers, nestin and CD133.
The site of GKS treatment failure was local in 16 (76.2%) of 21 patients with glioblastomas showing progression; in 9 of these 16 patients, the recurrence clearly arose within the target lesion of GKS. Histopathological examination after GKS and EBRT showed variable mixtures of viable tumor tissues and necrosis. Viable tumor tissues exhibited high MIB-1 indices but reduced numbers of tumor blood vessels. There was marked accumulation of CD133-positive glioma cells, particularly in remnant tumors within the necrotic areas, in sections obtained after GKS plus EBRT, whereas CD133-positive cells appeared very infrequently in primary sections prior to adjuvant treatment.
The results indicate that CD133-positive glioma stemlike cells can survive high-dose irradiation, leading to recurrence, despite prolonged damage to tumor blood vessels. This could be an essential factor limiting the effectiveness of GKS plus EBRT for malignant gliomas.
最近的证据表明，神经胶质瘤干细胞亚群可能有助于恶性神经胶质瘤的放射抵抗。为了验证这一假说，作者研究了经伽玛刀手术（GKS）和外束放射治疗（EBRT）高剂量照射后复发性恶性神经胶质瘤的组织病理学变化。
32 例恶性神经胶质瘤患者（8 例 3 级，24 例 4 级）接受 GKS 联合 EBRT。采用连续磁共振和 L-[甲基-（11）C]蛋氨酸 PET 图像评估 GKS 后残留或复发性肿瘤。12 例患者在 GKS 和 EBRT 后接受手术切除。组织切片进行 MIB-1、VIII 因子和干细胞标志物巢蛋白和 CD133 的免疫组织化学染色。
21 例胶质母细胞瘤患者中有 16 例（76.2%）GKS 治疗失败部位为局部，其中 16 例中有 9 例复发明显发生在 GKS 的靶病灶内。GKS 和 EBRT 后组织病理学检查显示活肿瘤组织和坏死的不同混合。活肿瘤组织表现出高 MIB-1 指数，但肿瘤血管数量减少。在 GKS 加 EBRT 后获得的切片中，CD133 阳性胶质细胞瘤细胞明显积聚，尤其是在坏死区域内的残留肿瘤中，而在辅助治疗前的原发性切片中，CD133 阳性细胞出现得非常罕见。
这些结果表明，CD133 阳性神经胶质瘤干细胞样细胞可以在高剂量照射下存活，导致复发，尽管肿瘤血管受到长期损害。这可能是限制 GKS 加 EBRT 治疗恶性神经胶质瘤效果的一个重要因素。
