Clinicopathological significance of MMP-2 and its specific inhibitor TIMP-2 in gastric cancer
Clinicopathological significance of MMP-2 and its specific inhibitor TIMP-2 in gastric cancer
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DOI：
10.14670/hh-23.917
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发表时间：
2008-08-01
影响因子：
2
通讯作者：
Moenig, S. P.
中科院分区：
文献类型：
--
作者：
Alakus, H.;Grass, G.;Moenig, S. P.
基质金属蛋白酶(MMPs)能降解细胞外基质和基底膜上的IV型胶原，在肿瘤细胞的迁移过程中起关键作用。在体内，MMPs被金属蛋白酶组织抑制物(TIMPs)所抑制。由于我们在先前的研究中发现基质金属蛋白酶-2的表达与胃癌的临床病理参数相关，所以我们现在研究了基质金属蛋白酶-2和基质金属蛋白酶-2的表达与胃癌患者生存的可能相关性，以及基质金属蛋白酶-2与临床病理参数的可能相关性。免疫组织化学染色检测MMP2和TIMP-2的表达，并进行半定量评分(0~3分)。用Kaplan-Meier对数列统计方法(对数列统计法)，上皮性基质金属蛋白酶-2高表达与肿瘤分期和生存不良显著相关。然而，经COX回归分析，高上皮性基质金属蛋白酶-2免疫反应不是一个独立的预后因素。TIMP-2在胃癌中的表达与生存无关，但TIMP-2在肿瘤细胞中的表达强度与WHO、Lauren和Ming的肿瘤分化程度以及有无远处转移显著相关。我们的研究结果表明，尽管不是一个独立的预后因素，但上皮性MMP2的高表达与胃癌的生存不良有关，而侵袭性形式的胃癌与TIMP-2的低表达有关。
Matrix metalloproteinases ( MMPs) can degrade type IV collagen of extracellular matrices and basal membranes and thus play a key role in the migration of malignant cells. In vivo, MMPs are inhibited by tissue inhibitors of metalloproteinases (TIMPs). Since in a previous study we showed that the expression of MMP-2 correlates with clinicopathological parameters in gastric cancer, we have now investigated a possible correlation of MMP-2 and TIMP-2 expression with survival in gastric cancer, as well as the possible association of TIMP-2 with clinicopathological parameters.Tissue samples were obtained from 116 gastric cancer patients who underwent gastrectomy with extended lymphadenectomy. MMP-2 and TIMP-2 expression was analysed using immunohistochemical staining and was graded semiquantitatively (score 0-3). High epithelial MMP-2 immunoreactivity was significantly associated with tumor stage and poor survival using the Kaplan-Meier log-rank statistical method (log-rank statistics). However, using Cox regression analysis, high epithelial MMP-2 immunoreactivity was not an independent prognostic factor. TIMP-2 showed no association with survival in gastric cancer, but the intensity of TIMP-2 staining in tumor cells correlated significantly with tumor differentiation based on the WHO and Lauren and Ming classifications, as well as with presence of distant metastasis.Our results show that high epithelial MMP-2 expression in gastric cancer is associated with poor survival, although it is not an independent prognostic factor, and that aggressive forms of gastric cancer are associated with low TIMP-2 expression.