Lim Michael, Guccione Samira, Haddix Terri, Sims Leroy, Cheshier Samuel, Chu Pauline, Vogel Hannes, Harsh Griffith
Department of Neurosurgery, Stanford University School of Medicine, Stanford, CA 94305, USA.
Hum Pathol. 2005 Jun;36(6):665-9. doi: 10.1016/j.humpath.2005.03.014.
alpha(v)beta(3) Is an integrin specifically expressed in endothelial cells of newly forming blood vessels. Integrin-mediated angiogenesis is hypothesized to play a central role in the development and the progression of central nervous system neoplasms. Accordingly, it is considered a potential target for antiangiogenic therapy. In the current study, we compare the expression of alpha(v)beta(3) in ependymomas, oligodendrogliomas, pilocytic astrocytomas, medulloblastomas, and vestibular schwannomas (acoustic neuromas). Samples of 5 tumors of each of the 5 tumor types were harvested surgically and frozen. After the pathological diagnosis was confirmed, immunohistochemistry was performed using an anti- alpha(v)beta(3) monoclonal antibody (LM609). The expression of alpha(v)beta(3) was assessed using a 4-tiered (0-3) grading scheme reflecting the percentage of positively staining vessels. All vestibular schwannomas demonstrated strong (grade 3) alpha(v)beta(3) expression. The expression was uniformly prominent in Antoni B regions of the tumors. Of 5 ependymomas, 4 demonstrated uniformly strong alpha(v)beta(3). Oligodendrogliomas, medulloblastomas, and pilocytic astrocytomas demonstrated more variable alpha(v)beta(3). alpha(v)beta(3) may contribute significantly to angiogenesis in vestibular schwannomas and ependymomas. Despite the high vascular density of oligodendrogliomas, pilocytic astrocytomas, and medulloblastomas, these tumors had variable moderate alpha(v)beta(3) expression. This discrepancy suggests temporal and/or regional variability in the angiogenesis in these types of tumor. This study provides the first demonstration of alpha(v)beta(3) expression in vestibular schwannomas, medulloblastomas, and pilocytic astrocytomas.
α(v)β(3)是一种特异性表达于新生血管内皮细胞的整合素。整合素介导的血管生成被认为在中枢神经系统肿瘤的发生和发展中起核心作用。因此，它被视为抗血管生成治疗的潜在靶点。在本研究中，我们比较了α(v)β(3)在室管膜瘤、少突胶质细胞瘤、毛细胞型星形细胞瘤、髓母细胞瘤和前庭神经鞘瘤（听神经瘤）中的表达情况。手术切除5种肿瘤类型中每种肿瘤的5个样本并冷冻保存。病理诊断确认后，使用抗α(v)β(3)单克隆抗体（LM609）进行免疫组织化学检测。采用4级（0 - 3）分级方案评估α(v)β(3)的表达，该方案反映阳性染色血管的百分比。所有前庭神经鞘瘤均显示α(v)β(3)强表达（3级）。肿瘤的Antoni B区表达均一致显著。5例室管膜瘤中，4例显示α(v)β(3)一致强表达。少突胶质细胞瘤、髓母细胞瘤和毛细胞型星形细胞瘤的α(v)β(3)表达则更具变异性。α(v)β(3)可能在前庭神经鞘瘤和室管膜瘤的血管生成中起重要作用。尽管少突胶质细胞瘤、毛细胞型星形细胞瘤和髓母细胞瘤的血管密度较高，但这些肿瘤的α(v)β(3)表达呈中度且有变化。这种差异表明这些类型肿瘤的血管生成存在时间和/或区域变异性。本研究首次证实了α(v)β(3)在前庭神经鞘瘤、髓母细胞瘤和毛细胞型星形细胞瘤中的表达。
