Friedberg M H, Glantz M J, Klempner M S, Cole B F, Perides G
Department of Medicine, Tupper Research Institute, New England Medical Center, Boston, Massachusetts 02111, USA.
Cancer. 1998 Mar 1;82(5):923-30. doi: 10.1002/(sici)1097-0142(19980301)82:5<923::aid-cncr18>3.0.co;2-2.
Detection in tumor tissue of specific matrix metalloproteinases (MMPs), particularly gelatinases A and B, correlates with the grade and aggressiveness of primary and metastatic brain tumors. The ability to detect these enzymes in the cerebrospinal fluid (CSF) would be a minimally invasive method of evaluating brain tumors.
CSF from 66 patients with white blood cell counts of < or = 5 microL were analyzed for the presence of gelatinolytic activity by zymography. Twenty-nine patients had malignant astrocytomas, 10 had brain metastases from systemic malignancies, 4 had systemic cancer not involving the central nervous system, 4 had nonmalignant neurologic diseases, and 19 were healthy controls. Fifteen CSF samples had positive cytologies. The zymographic results were retrospectively correlated with clinical information and CSF cytologic data.
CSF from all patients with malignant astrocytomas or brain metastases contained precursor gelatinase A (pMMP2) and precursor gelatinase B (pMMP9), whereas control CSF contained only pMMP2. All patients with positive CSF cytologies had activated MMP2. A similar correlation was observed between the presence of activated MMP9 and positive CSF cytology.
The precursor and activated forms of gelatinases A and B can be detected in the CSF of patients with primary and metastatic brain tumors. The distribution of gelatinase activity in CSF distinguishes patients with malignant gliomas or brain metastases from those without brain tumors, and distinguishes patients with meningeal carcinomatosis from those without CSF spread of tumor, regardless of their brain tumor status. Analysis of MMPs in the CSF may be a sensitive technique for diagnosing CNS tumors and provide an early indication of tumor recurrence. This technique may also provide longitudinal information that would be useful in evaluating ongoing treatment and predicting tumor behavior.
在肿瘤组织中检测特定的基质金属蛋白酶（MMPs），尤其是明胶酶A和B，与原发性和转移性脑肿瘤的分级及侵袭性相关。在脑脊液（CSF）中检测这些酶的能力将是一种评估脑肿瘤的微创方法。
对66例白细胞计数≤5/μL的患者的脑脊液进行酶谱分析，以检测明胶酶活性。其中29例患有恶性星形细胞瘤，10例有系统性恶性肿瘤的脑转移，4例患有不涉及中枢神经系统的系统性癌症，4例患有非恶性神经疾病，19例为健康对照。15份脑脊液样本细胞学检查呈阳性。酶谱分析结果与临床信息和脑脊液细胞学数据进行回顾性关联。
所有恶性星形细胞瘤或脑转移患者的脑脊液中均含有前体明胶酶A（pMMP2）和前体明胶酶B（pMMP9），而对照脑脊液中仅含有pMMP2。所有脑脊液细胞学检查阳性的患者均有活化的MMP2。活化的MMP9的存在与脑脊液细胞学阳性之间也观察到类似的相关性。
在原发性和转移性脑肿瘤患者的脑脊液中可检测到明胶酶A和B的前体及活化形式。脑脊液中明胶酶活性的分布可将恶性胶质瘤或脑转移患者与无脑部肿瘤的患者区分开来，并将脑膜癌病患者与无肿瘤脑脊液播散的患者区分开来，无论其脑部肿瘤状态如何。脑脊液中MMPs的分析可能是诊断中枢神经系统肿瘤的一种敏感技术，并可提供肿瘤复发的早期迹象。该技术还可能提供有助于评估正在进行的治疗和预测肿瘤行为的纵向信息。
