人幕上星形细胞瘤肿瘤血管中内皮型一氧化氮合酶的表达与恶性程度相关。

Endothelial nitric oxide synthase expression in tumor vasculature is correlated with malignancy in human supratentorial astrocytic tumors.

作者信息

Iwata S, Nakagawa K, Harada H, Oka Y, Kumon Y, Sakaki S

机构信息

Department of Neurological Surgery, Ehime University School of Medicine, Japan.

出版信息

Neurosurgery. 1999 Jul;45(1):24-8; discussion 29. doi: 10.1097/00006123-199907000-00006.

DOI:10.1097/00006123-199907000-00006

PMID:10414562

Abstract

OBJECTIVE

Endothelial nitric oxide synthase (eNOS) may play an important role in the regulation of tumor blood flow and vascular permeability. However, there have been no reports describing alterations of eNOS expression in relation to malignant progression in human astrocytic tumors. We immunohistochemically studied the relationship between eNOS expression in tumor vasculature and malignancy in supratentorial astrocytic tumors.

METHODS

Tissue samples were obtained from 12 patients with low-grade astrocytomas, 10 with anaplastic astrocytomas, and 17 with glioblastomas. Normal brain tissue samples were obtained from four patients with other brain diseases. Immunohistochemical staining was performed using the avidin-biotin complex method, with polyclonal anti-eNOS antibody, and the levels of eNOS expression in endothelial cells were evaluated as slight, moderate, or intense on the basis of eNOS immunoreactivity. The proliferative potential was assessed as the MIB-1 staining index for tumor cells.

RESULTS

The expression of eNOS was slight in all specimens of normal brain tissue, slight in 7 and moderate in 5 specimens of low-grade astrocytoma, slight in 2, moderate in 6, and intense in 2 specimens of anaplastic astrocytoma, and moderate in 5 and intense in 12 specimens of glioblastoma. The MIB-1 staining index (mean+/-standard deviation) was 0.2+/-0.2% for normal specimens, 1.8+/-0.6% for low-grade astrocytomas, 9.6+/-6.9% for anaplastic astrocytomas, and 18.5+/-7.7% for glioblastomas. The MIB-1 staining indices for slight, moderate, and intense eNOS expression were 2.0+/-2.3%, 10.8+/-9.8%, and 16.9+/-7.7%, respectively.

CONCLUSION

Expression of eNOS in tumor vessels was significantly correlated with histological grade and proliferative potential. These findings suggest that astrocytic tumor vessels possess higher activity for nitric oxide production than do normal vessels.

摘要

目的

内皮型一氧化氮合酶（eNOS）可能在肿瘤血流和血管通透性调节中发挥重要作用。然而，尚无关于人类星形细胞瘤中eNOS表达变化与恶性进展关系的报道。我们采用免疫组织化学方法研究幕上星形细胞瘤肿瘤血管中eNOS表达与恶性程度之间的关系。

方法

从12例低级别星形细胞瘤、10例间变性星形细胞瘤和17例胶质母细胞瘤患者中获取组织样本。从4例患有其他脑部疾病的患者中获取正常脑组织样本。采用抗生物素蛋白-生物素复合物法，使用多克隆抗eNOS抗体进行免疫组织化学染色，并根据eNOS免疫反应性将内皮细胞中eNOS表达水平评估为轻度、中度或重度。将增殖潜能评估为肿瘤细胞的MIB-1染色指数。

结果

正常脑组织所有标本中eNOS表达均为轻度，低级别星形细胞瘤标本中7例为轻度、5例为中度，间变性星形细胞瘤标本中2例为轻度、6例为中度、2例为重度，胶质母细胞瘤标本中5例为中度、12例为重度。正常标本的MIB-1染色指数（平均值±标准差）为0.2±0.2%，低级别星形细胞瘤为1.8±0.6%，间变性星形细胞瘤为9.6±6.9%，胶质母细胞瘤为18.5±7.7%。eNOS轻度、中度和重度表达的MIB-1染色指数分别为2.0±2.3%、10.8±9.8%和16.9±7.7%。