Expression of matrix metalloproteinases and their inhibitors in medulloblastomas and their prognostic relevance
Expression of matrix metalloproteinases and their inhibitors in medulloblastomas and their prognostic relevance
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DOI：
10.1158/1078-0432.ccr-0625-03
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发表时间：
2004-07-15
影响因子：
11.5
通讯作者：
Herms, J
中科院分区：
文献类型：
--
作者：
Özen, Ö;Krebs, B;Herms, J
目的和实验设计：导致髓母细胞瘤（MB）（儿童最常见的恶性脑肿瘤）转移性疾病的细胞机制目前尚不清楚。然而，最近有人提出基质金属蛋白酶（MMP）的参与。我们检查了四种 MMP（MMP-2 和 -9、膜型 1 和 2 MMP（MT1- 和 MT2-MMP））的表达和定位，并将这些数据与其主要抑制剂、金属蛋白酶组织抑制剂（TIMP-1、-2 和 -3）在 83 个经典 Mill 和 18 个促结缔组织中进行关联。 结果：独立于组织学亚型， 在一小部分肿瘤中发现了 MMP-2 表达，而 MMP-9 和 MT1- 或 MT2-MMP 在 > 75% 的肿瘤样本中表达。另一方面，TIMP-1、-2 和 -3 的表达被发现取决于组织学亚型：TIMP-3 经常在经典 MB 中发现，而 TIMP-2 经常在促纤维增生性 MB 中表达 (P = 0.007-0.001)。此外，TIMP-3和-2均与除MMP-2外所有研究的金属蛋白酶的表达显着相关。 TIMP-1 仅在经典 MB 中以较低比例检测到，是唯一与 MMP-2 表达相关的 TIMP。 Kaplan-Meier 估计显示，肿瘤样本中 MMP 强表达的患者的长期生存率显着降低。然而，在多变量logistic回归分析中，预后仅由临床参数显着决定。结论：TIMP-3和-2表达与MB的组织学亚型高度相关，并且与某些MMP的表达密切相关。然而，TIMP 和 MMP 的表达并不能独立于临床参数来确定预后。
Purpose and Experimental Design: The cellular mechanisms leading to metastatic disease in medulloblastoma (MB), the most common malignant brain tumor in childhood, are mainly unknown. Recently, however, the involvement of matrix metalloproteinases (MMPs) has been suggested. We examined the expression and localization of four MMPs-MMP-2 and -9, membrane-type 1 and 2 MMP (MT1- and MT2-MMP)-and correlated the data with those for their main inhibitors, tissue inhibitors of metalloproteinases (TIMP-1, -2, and -3), in 83 classical and 18 desmoplastic Mills.Results: Independent of the histological subtype, MMP-2 expression was found in a small percentage of tumors, whereas MMP-9 and MT1- or MT2-MMP were expressed in >75% of tumor samples. The expression of TIMP-1, -2, and -3, on the other hand, was found to depend on the histological subtype: TIMP-3 was often found in classical MB, whereas TIMP-2 was often expressed in desmoplastic MB (P = 0.007-0.001). In addition, both TIMP-3 and -2 correlated significantly with the expression of all studied metalloproteinases except MMP-2. TIMP-1, detected only in classical MB in a low percentage, was the only TIMP that correlated with the expression of MMP-2. Kaplan-Meier estimation revealed significantly reduced long-term survival of patients with strong MMP expression in tumor samples. In multivariate logistic regression analysis, however, the prognosis was significantly determined only by clinical parameters.Conclusions: TIMP-3 and -2 expression is highly correlated with histological subtypes of MBs and strongly associated with the expression of certain MMPs. The expression of TIMPs and MMPs, however, does not determine prognosis independently of clinical parameters.