Immunohistochemical study of MT-MMP tissue status in gastric carcinoma and correlation with survival analyzed by univariate and multivariate analysis
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1Surgery II, School of Medicine, Kanazawa University, Kanazawa City, Ishikawa Ken 920, Japan.
Abstract:
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.
Insights
Matrix metalloproteinase (MMP) expression, specifically membrane type (MT-MMP), is linked to advanced gastric cancer. MT-MMP presence indicates a worse prognosis and higher metastatic potential in patients.
Area of Science:
- Oncology
- Cancer Biology
- Biochemistry
Background:
- Matrix metalloproteinases (MMPs) are implicated in advanced cancer stages, driving tumor progression, invasion, and metastasis.
- Membrane type matrix metalloproteinases (MT-MMPs) possess a transmembrane domain and activate pro-MMP-2, crucial for extracellular matrix degradation.
- MT-MMP expression on invasive tumor cells facilitates pericellular matrix degradation and enhances cancer cell invasiveness.
Purpose of the Study:
- To investigate the correlation between MT-MMP expression and metastasis in gastric cancer.
- To determine the relationship between MT-MMP expression and patient prognosis in gastric cancer.
Main Methods:
- Immunohistochemical analysis of MT-MMP expression in 127 primary gastric tumors.
- Correlation of MT-MMP immunoreactivity with clinicopathological prognostic parameters and patient survival data.
Main Results:
- MT-MMP was detected in 57% of gastric tumors, primarily on the cell membrane of cancer cells and fibroblasts at the invasion front.
- MT-MMP expression was significantly associated with advanced tumor features: invasive type, lymph node involvement, lymphatic invasion, vessel invasion, and peritoneal dissemination.
- Patients with MT-MMP-positive tumors exhibited a significantly worse prognosis compared to MT-MMP-negative cases (p<0.001).
Conclusions:
- MT-MMP overexpression is an independent prognostic factor in gastric cancer.
- Immunohistochemical detection of MT-MMP may serve as a valuable indicator of metastatic potential and prognosis for gastric cancer patients.