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 metastasis. 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 the 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 between MT-MMP expression and metastasis and prognosis in gastric cancer patients, MT-MMP expression was analyzed immunohistochemically in 127 primary tumors and results were correlated with several prognostic parameters and patient's survival. MT-MMP immunoreactivity was stained on the cell membrane of cancer cells and fibroblasts in the invasion front. MT-MMP was detected in 72 tumors (57%) (MT-MMP-positive). MT-MMP expression was closely associated with macroscopically invasive type, nodal involvement, lymphatic invasion, vessel invasion, and peritoneal dissemination. Patients with MT-MMP-positive tumor had a significantly worse prognosis than those with MT-MMP-negative tumor (p<0.001). Multivariate analysis showed MT-MMP overexpression as an independent prognostic factor in gastric cancer patients. Immunohistochemical analysis for MT-MMP may be an indicator of metastatic potential or the prognosis of gastric cancer patients.
Surgery II, School of Medicine, Kanazawa University, Kanazawa City, Ishikawa Ken 920, Japan.
E
E
Bando
Y
Y
Yonemura
Y
Y
Endou
T
T
Sasaki
K
K
Taniguchi
H
H
Fujita
S
S
Fushida
T
T
Fujimura
G
G
Nishimura
K
K
Miwa
M
M
Seiki
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D005109:Extracellular Matrix / Q000201:enzymology; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000473:pathology / Q000556:secondary; D008207:Lymphatic Metastasis; D008666:Metalloendopeptidases / Q000032:analysis / Q000378:metabolism*; D008875:Middle Aged; D015999:Multivariate Analysis; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D010534:Peritoneal Neoplasms / Q000473:pathology / Q000556:secondary; D011379:Prognosis; D013274:Stomach Neoplasms / Q000201:enzymology* / Q000401:mortality / Q000473:pathology*; D016019:Survival Analysis; D013997:Time Factors
D008666:Metalloendopeptidases