METHODS: To further clarify the clinical significance of
TIMP-1, the authors used an
enzyme-linked immunoassay to assess
TIMP-1 protein concentrations in samples of
tumor tissue from 86 patients who underwent primary resection for gastric
carcinoma. Concentrations in samples of normal gastric mucosa from 73 of these patients also were assessed.
RESULTS: Tissue
TIMP-1 concentrations were significantly greater in gastric
tumors than in normal gastric mucosa and were associated significantly with a variety of pathologic factors, including macroscopic type, depth of
tumor invasion in the gastric wall, presence of lymphatic vessel invasion, pattern of
tumor infiltration into the surrounding tissue, and disease stage. Significantly greater
TIMP-1 concentrations were found in
tumors that were exposed to the serosal surface compared with
tumors that were limited to the submucosal layer.
TIMP-1 protein was significantly greater in
tumors with lymphatic vessel invasion, an infiltrative pattern into the surrounding tissue (INF-gamma), and in
tumors from patients with Stage III disease. Survival was significantly poorer in patients with
TIMP-1 concentrations > or = 10.0 ng/mg total
protein. When patients were stratified by disease stage, survival was significantly different in patients with Stage III disease. Multivariate analysis demonstrated that intratumoral concentrations of
TIMP-1 were the most significant independent factor for survival.
CONCLUSIONS: