基质金属蛋白酶-2、金属蛋白酶组织抑制因子-2表达与滑膜肉瘤转移、肿瘤血管生成的关系及其预后意义

目的探讨滑膜肉瘤肿瘤细胞中基质金属蛋白酶-2（MMP-2）和金属蛋白酶组织抑制因子-2（TIMP-2）的表达情况及其预后意义。方法采用免疫组织化学SP法检测72例滑膜肉瘤肿瘤细胞中MMP-2、TIMP-2的表达情况,收集每例临床病理学参数并统计生存率、以CD31标记检测微血管密度（MVD）并分析与生存率的关系。结果（1）MMP-2、TIMP-2的表达阳性率分别为84．7％（61／72）和83．3％（60／72）,二者表达强度呈负相关关系（r=-0．290,P=0．013）。（2）有转移病例出现MMP-2高表达和TIMP-2低表达的比例明显高于无转移病例（分别P=0．010,P=0．002）。（3）MMP-2高表达病例的MVD明显大于其低表达者（P=0．005）,TIMP-2高表达病例的MVD明显小于其低表达者（P=0．048）。（4）单因素和多因素生存分析均显示TIMP-2低表达与患者预后不良有关（分别P=0．002,P=0．016）。结论MMP-2和TIMP-2表达异常可能与滑膜肉瘤的转移及肿瘤血管生成有关,TIMP-2低表达可能提示患者预后不良。

Correlation between matrix metalloproteinases-2 and tissue inhibitor of metalloproteinase-2 expression, metastatic potential and tumor angiogenesis in synovial sarcoma and its prognostic significance

Objective To study the expression of matrix metalloproteinases (MMP)-2 and tissue inhibitor of metalloproteinase(TIMP)-2 in tumor cells of synovial sarcoma and its clinical significance. Methods Expression of MMP-2 and TIMP-2 in tumor cells of 72 cases of synovial sarcoma was studied by immunohistochemistry. The profile was correlated with clinicopathologic parameters, microvessel density (MVD) (analyzed by CD31 immunostaining) and survival rate. Results (1) There was a statistically significant negative correlation between expression of MMP-2 and TIMP-2 (r=-0.290 and P=0.013). (2) The proportion of high MMP-2 expression to low TIMP-2 expression in patients with tumor metastasis was significantly higher than that in patients without metastasis (P=0.010 and 0.002 respectively). (3) MVD of patients with high MMP-2 expression was higher than that in the low MMP-2 expression group (P=0.005). MVD of patients with high TIMP-2 expression was lower than that in the low TIMP-2 expression group (P=0.048). (4) Low TIMP-2 expression significantly correlated with poor prognosis of patients with synovial sarcoma, by univariate and multivariate survival analysis (P=0.002 and 0.016 respectively). Conclusions Expression of MMP-2 and TIMP-2 correlates with metastatic potential and tumor angiogenesis in synovial sarcoma. Low TIMP-2 expression often indicates poor prognosis and unfavorable clinical outcomes.