Clinicopathological significance of MMP-2 and its specific inhibitor TIMP-2 in gastric cancer.

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.