J Korean Med Sci.  1999 Aug;14(4):417-423. 10.3346/jkms.1999.14.4.417.

Role of tissue inhibitors of metalloproteinases (TIMPs) in colorectal carcinoma

• Joo YE
• Seo KS
• Kim J
• Kim HS
• Rew JS
• Park CS
• Kim SJ

• KMID: 1731316
• DOI: http://doi.org/10.3346/jkms.1999.14.4.417

Abstract

Increased production of matrix metalloproteinases (MMPs) has been associated with increases in invasive and metastatic potential in many types of human carcinoma. Tissue inhibitors of metalloproteinase (TIMP)-1 inhibits most interstitial collagenases and MMP-9. TIMP-2 binds specifically and noncovalently to the pro-form of MMP-2 and inhibits its enzyme activity. In this study, we examined TIMP-1 and TIMP-2 expressions in relation to clinicopathological variables in colorectal carcinoma with in situ hybridization and immunohistochemistry. TIMP-1 and TIMP-2 expressions were localized overwhelmingly to pericancer stromal cells, while malignant and normal mucosal cells were weak or negative. Strong stromal TIMP-1 immunoreactivity correlated with Dukes' stage (p=0.022), status of lymph node metastasis (p=0.044) and poor survival (p= 0.005). The degree of immunohistochemical staining of TIMP-2 did not correlate with all clinicopathological variables. The correlation between enhanced TIMP-1 expression and advanced stage and poor survival suggest a growth promoting activity of TIMP-1 in colorectal carcinoma.

Keyword

Tissue inhibitors of metalloproteinases; Colorectal neoplasms; Immunohistochemistry; In situ hybridization

MeSH Terms

Adenocarcinoma/pathology
Adenocarcinoma/mortality
Adenocarcinoma/enzymology*
Adult
Aged
Aged, 80 and over
Antibodies
Collagenases/immunology
Collagenases/genetics*
Collagenases/analysis
Colorectal Neoplasms/pathology
Colorectal Neoplasms/mortality
Colorectal Neoplasms/enzymology*
DNA Probes
Female
Gelatinase A
Gelatinase B
Gelatinases/immunology
Gelatinases/genetics*
Gelatinases/analysis
Gene Expression Regulation, Enzymologic
Gene Expression Regulation, Neoplastic
Human
In Situ Hybridization
Male
Metalloendopeptidases/immunology
Metalloendopeptidases/genetics*
Metalloendopeptidases/analysis
Middle Age
Predictive Value of Tests
RNA, Messenger/analysis
Stromal Cells/pathology
Stromal Cells/enzymology
Survival Analysis
Tissue Inhibitor-of Metalloproteinase-2/immunology
Tissue Inhibitor-of Metalloproteinase-2/genetics*
Tissue Inhibitor-of Metalloproteinase-2/analysis
Tissue-Inhibitor of Metalloproteinase-1/immunology
Tissue-Inhibitor of Metalloproteinase-1/genetics*
Tissue-Inhibitor of Metalloproteinase-1/analysis