BACKGROUND: Matrix metalloproteinase 9 (MMP-9) facilitates tumor invasion and metastasis via basement membrane degradation. Control of MMP-9 production by cancer-stromal cell interactions in these processes has been observed.METHODS: We measured plasma MMP-9 concentrations, using a one-step sandwich enzyme immunoassay, and also immunohistochemically localized MMP-9 in patients with small gastric cancers limited to the mucosa. The cancers were classified as intraepithelial tumor (Tis) and T1 disease according to the tumor-node-metastasis (TNM) classification of the International Union Against Cancer.RESULTS: Patients with T1 disease had a higher positivity rate for and mean value of MMP-9 than patients with Tis disease. In T1 tumors, MMP-9 expression determined immunohistochemically, was greater in cells in cancer stroma than in cells in noncancerous stroma, a situation found in only a few Tis tumors.CONCLUSIONS: These results suggest that MMP-9 is related to the initial step of gastric cancer invasion.