Abstract
4062 Background: Tissue inhibitor of metalloproteinase-1 (TIMP-1) not only inhibits matrix metalloproteinases but also promotes cell proliferation and inhibits apoptosis. Clinically, TIMP-1 in the tumor and plasma has been reported to correlate with disease progression and prognosis in patients with various types of malignancy. Methods: To clarify the prognostic implication of plasma TIMP-1 in gastric cancer, 149 patients with primary tumors were studied preoperatively and were followed-up for more than 5 years (Median =63.0: range 60–104 months). Staging was done by UICC-TNM and plasma TIMP-1 ≥112.5 ng/mg protein were defined as positive. Results: Thirty of 149 patients had positive TIMP-1 (20.1%). Between patients with negative and positive TIMP-1, significant differences were observed in age, T, N, M, and stage of the disease. Also by univariate analysis, T, N, M, and plasma TIMP-1 were related with survival. Multivariate analysis demonstrated that T, N, and plasma TIMP-1 were significant prognosticators with hazard ratio of 2.251 (p=0.000), 1.596 (p=0.002), and 3.135(p=0.000), respectively; and in M0 tumors they were 2.640 (p=0.000), 1.532 (p=0.034), and 3.385 (p=0.002), respectively. When the survival was stratified by N category and stage, 5-year survival rates of negative and positive TIMP-1 were 94.3% (n=70) and 87.5% (n=8) in N0 (ns), 61.5% (n=30) and 0% (n=6) in N1 (p=0.000), 50% (n=10) and 0% (n=5) in N2 (p=0.031), and 22.2% (n=9) and 9.1% (n=11) in N3 (p=0.042), respectively, while those were 95.6% (n=68) and 87.5% (n=8) in stage I (ns), 75% (n=20) only for negative in stage II, 51.5% (n=17) and 0% (n=7) in stage III (p=0.003), and 21.4% (n=14) and 6.7% (n=15) in stage IV (p=0.03), respectively. Conclusions: These results suggested that plasma TIMP-1 was an independent significant prognosticator in patients with gastric cancer and would identify a more aggressive subset of the node positive and advanced disease. No significant financial relationships to disclose.
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