title: Role of tissue inhibitors of metalloproteinases (TIMPs) in colorectal carcinoma.
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.
authors.affiliation: Department of Internal Medicine, Chonnam National University Medical School, Kwangju, Korea.
authors.forename: Y E
authors.initials: YE
authors.lastname: Joo
authors.forename: K S
authors.initials: KS
authors.lastname: Seo
authors.forename: J
authors.initials: J
authors.lastname: Kim
authors.forename: H S
authors.initials: HS
authors.lastname: Kim
authors.forename: J S
authors.initials: JS
authors.lastname: Rew
authors.forename: C S
authors.initials: CS
authors.lastname: Park
authors.forename: S J
authors.initials: SJ
authors.lastname: Kim
mesh_terms: D000230:Adenocarcinoma / Q000201:enzymology* / Q000401:mortality / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000906:Antibodies; D017364:Collagenases / Q000032:analysis / Q000235:genetics* / Q000276:immunology; D015179:Colorectal Neoplasms / Q000201:enzymology* / Q000401:mortality / Q000473:pathology; D015342:DNA Probes; D005260:Female; D018093:Gelatinases / Q000032:analysis / Q000235:genetics* / Q000276:immunology; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D017403:In Situ Hybridization; D008297:Male; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D008666:Metalloendopeptidases / Q000032:analysis / Q000235:genetics* / Q000276:immunology; D008875:Middle Aged; D011237:Predictive Value of Tests; D012333:RNA, Messenger / Q000032:analysis; D017154:Stromal Cells / Q000201:enzymology / Q000473:pathology; D016019:Survival Analysis; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000032:analysis / Q000235:genetics* / Q000276:immunology; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000032:analysis / Q000235:genetics* / Q000276:immunology
chemical_list: D000906:Antibodies; D015342:DNA Probes; D012333:RNA, Messenger; D019715:Tissue Inhibitor of Metalloproteinase-1; D019716:Tissue Inhibitor of Metalloproteinase-2; D017364:Collagenases; D018093:Gelatinases; D008666:Metalloendopeptidases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9