Mikkelsen T, Yan P S, Ho K L, Sameni M, Sloane B F, Rosenblum M L
Department of Neurosurgery, Neurology, Henry Ford Hospital, Detroit, Michigan, USA.
J Neurosurg. 1995 Aug;83(2):285-90. doi: 10.3171/jns.1995.83.2.0285.
The poor prognosis of patients with malignant gliomas is at least partially due to the invasive nature of these tumors. In this study, the authors investigated the possibility that the cysteine protease cathepsin B (CB) is a participant in the process of glial tumor cell invasion. To accomplish this, an immunohistochemical analysis was made of the localization of antibodies to CB in biopsies of five specimens of normal brain, 16 astrocytomas, 33 anaplastic astrocytomas, and 33 glioblastomas multiforme. Staining was scored according to the percentage of positive cells and the intensity of the stain, graded from 0 to 3+. Staining for CB was not seen in any of five samples of normal brain except for occasional neuronal cell bodies and microglia. Only five (31%) of 16 astrocytomas showed a small percentage of positive cells (0.01%-3%) that were stained in a light, diffuse cytoplasmic pattern (1+). Twenty-nine (87.8%) of 33 anaplastic astrocytomas showed positive light, granular staining in 2% to 40% of cells. In anaplastic astrocytoma, the staining within a tumor was heterogeneous with intensities of 1+ (17%), 1+ to 2+ (29%), or 2+ (55%). In contrast, all 33 (100%) glioblastomas were positive in 10% to 90% of cells. The staining was present in a coarse, granular pattern with an intensity of 2+ (12%) or 3+ (88%). Tumor cells infiltrating into brain adjacent to malignant gliomas stained positively in 26 cases that could be evaluated for glioblastoma multiforme; these invading cells frequently followed penetrating blood vessels as typical "secondary structures of Scherer." Moderate to intense CB staining associated with endothelial proliferation in high-grade tumors was also observed, especially in regions of tumor infiltration into adjacent normal brain. These results provide evidence consistent with the hypothesis that CB is functionally significant in the process of tumor invasion and angiogenesis in the clinical progression of the malignant phenotype in astrocytes.
恶性胶质瘤患者预后较差，至少部分原因是这些肿瘤具有侵袭性。在本研究中，作者调查了半胱氨酸蛋白酶组织蛋白酶B（CB）参与胶质肿瘤细胞侵袭过程的可能性。为此，对5例正常脑组织活检标本、16例星形细胞瘤、33例间变性星形细胞瘤和33例多形性胶质母细胞瘤中CB抗体的定位进行了免疫组织化学分析。根据阳性细胞百分比和染色强度进行评分，分级为0至3+。除偶尔的神经元细胞体和小胶质细胞外，在5例正常脑样本中均未观察到CB染色。16例星形细胞瘤中只有5例（31%）显示少量阳性细胞（0.01%-3%），呈轻度、弥漫性胞质染色模式（1+）。33例间变性星形细胞瘤中有29例（87.8%）显示2%至40%的细胞呈阳性轻度颗粒状染色。在间变性星形细胞瘤中，肿瘤内的染色不均匀，强度为1+（17%）、1+至2+（29%）或2+（55%）。相比之下，所有33例（100%）胶质母细胞瘤在10%至90%的细胞中呈阳性。染色呈粗大颗粒状，强度为2+（12%）或3+（88%）。在26例可评估的多形性胶质母细胞瘤中，浸润到恶性胶质瘤邻近脑组织中的肿瘤细胞呈阳性染色；这些侵袭性细胞常沿着穿透性血管，呈典型的“Scherer二级结构”。在高级别肿瘤中还观察到与内皮细胞增殖相关的中度至强CB染色，尤其是在肿瘤浸润到邻近正常脑组织的区域。这些结果提供的证据与以下假设一致，即CB在星形细胞恶性表型临床进展中的肿瘤侵袭和血管生成过程中具有功能意义。
