IMMUNOHISTOCHEMICAL STUDY OF MT-MMP TISSUE STATUS IN GASTRIC-CARCINOMA AND CORRELATION WITH SURVIVAL ANALYZED BY UNIVARIATE AND MULTIVARIATE-ANALYSIS

Matrix metalloproteinase (MMP) expression is associated with advanced- stage cancer and contributes to tumor progression, invasion, and metas tasis. Membrane type matrix metalloproteinase (MT-MMP) has a potential transmembrane domain at the C terminus and activates pro-MMP-2, which is mainly produced from interstitial fibroblasts. Its expression on t he membrane of invasive tumor cells results in the pericellular space degradation at cell-matrix contact sites and renders cancer cells more invasive at the migration front. To elucidate the relationship betwee n MT-MMP expression and metastasis and prognosis in gastric cancer pat ients, MT-MMP expression was analyzed immunohistochemically in 127 pri mary tumors and results were correlated with several prognostic parame ters and patient's survival. MT-MMP immunoreactivity was stained on th e cell membrane of cancer cells and fibroblasts in the invasion front. MT-MMP was detected in 72 tumors (57%) (MT-MMP-positive). MT-MMP expr ession was closely associated with macroscopically invasive type, noda l involvement, lymphatic invasion, vessel invasion, and peritoneal dis semination. Patients with MT-MMP-positive tumor had a significantly wo rse prognosis than those with MT-MMP-negative tumor (p<0.001). Multiva riate analysis showed MT-MMP overexpression as an independent prognost ic factor in gastric cancer patients. Immunohistochemical analysis for MT-MMP may be an indicator of metastatic potential or the prognosis o f gastric cancer patients.