E. Bando et al., IMMUNOHISTOCHEMICAL STUDY OF MT-MMP TISSUE STATUS IN GASTRIC-CARCINOMA AND CORRELATION WITH SURVIVAL ANALYZED BY UNIVARIATE AND MULTIVARIATE-ANALYSIS, Oncology Reports, 5(6), 1998, pp. 1483-1488
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.