Usefulness of MMP-9/TIMP-1 in Predicting Tumor Recurrence in Patients Undergoing Curative Surgical Resection for Gastric Carcinoma

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Abstract
Degradation of the extracellular matrix is an essential step in tumor invasion and metastasis. It involves the actions of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs). We evaluated the expression of MMP-9 and TIMP-1 in gastric carcinomas and the relationship between this expression and tumor recurrence. Eighty patients who had undergone curative surgical resection for gastric carcinoma were included. Resected gastric tissue samples were stained immunohistochemically to evaluate the expression of MMP-9 and TIMP-1. TIMP-1 expression was related to the depth of tumor invasion and lymph node metastasis. The proportion of tumors larger than 5 cm, or displaying muscle layer invasion, and the cumulative incidence of tumor recurrence were significantly elevated in patients with tumors expressing TIMP-1. Furthermore, these measures were lowest in patients with no TIMP-1 expression and highest in patients who only expressed TIMP-1. In conclusion, TIMP-1 expression and the balance between expression of MMP-9 and expression of TIMP-1 may be important indicators of tumor progression and predictors of tumor recurrence.