MATRIX METALLOPROTEINASE-7 IS A USEFUL MARKER FOR PREDICTING AGGRESSIVE BEHAVIOR OF SUBMUCOSAL GASTRIC CANCER

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To elucidate the process of metastasis in submucosal gastric cancer (SM-GC), we examined the immunohistochemical expression of matrix metalloproteinases (MMPs: MMP-2, MMP-7, and MMP-9) and tissue inhibitors of metalloproteinases (TIMPs: TIMP-1, and TIMP-2) in 66 cases of SM-GC, and compared them with clinicopathological findings of the cases. The positive rates for MMP-2, MMP-7, MMP-9, TIMP-1, and TIMP-2 were 42.4%, 33.3%, 9.1%, 0%, and 48.5%, respectively. There was a significant correlation between MMP-7 positive rate and the degree of tumor invasion. Moreover, only MMP-7 positive rate was significantly higher in cases with lymphatic invasion, vascular vessel invasion, and lymph nodes metastasis than in cases without them. MMP-2 positive rate was significantly higher in cases with massive submucosal invasion (sm2) and intestinal-type carcinoma. There were no significant correlations between clinicopathological findings and positive rates for MMP-9, TIMP-1, and TIMP-2. In logistic regression, MMP-7 immunoreactivity was found to be an independent risk factor of lymphatic invasion, vascular vessel invasion, and lymph nodes metastasis. These data suggest that MMP-7 is an important factor implicated in local invasion and metastasis, and would be a useful marker for predicting aggressive behavior of SM-GC.