Role of tissue inhibitors of metalloproteinases (TIMPs) in colorectal carcinoma.
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.
Joo
Y E
YE
Department of Internal Medicine, Chonnam National University Medical School, Kwangju, Korea.
Seo
K S
KS
Kim
J
J
Kim
H S
HS
Rew
J S
JS
Park
C S
CS
Kim
S J
SJ
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
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