Low collagenase-1 (MMP-1) and MT1-MMP expression levels are favourable survival markers in advanced colorectal carcinoma.
OBJECTIVE
Extracellular matrix degradation is required for invasive growth and metastasis formation in colorectal carcinoma; therefore, we examined matrix metalloproteinases expression (MMP-1, MMP-13 and MT1-MMP) and apoptosis in tumours from 49 patients with advanced colorectal disease.


METHODS
MMP expression was determined immunohistochemically and apoptotic index (AI) was ascertained using the TUNEL assay.


RESULTS
Low levels of MT1-MMP, MMP-1 and AI were found to be favourable markers significantly associated with longer survival. MT1-MMP expression levels below the median (</=14.0% of tumour cells) were associated with better overall survival (median 26.2 vs. 15.6 months, p = 0.02) and MMP-1 expression levels below the median (</=28.7% of tumour cells) correlated with longer survival following metastasis (median 21.5 vs. 13.3 months, p = 0.05). MT1-MMP, MMP-1 and AI were all found to have significant independent effects on survival. Interestingly, MMP-1 expression levels above the median were associated with distal disease of the colon (p = 0.02).


CONCLUSIONS
These findings reveal that MT1-MMP and MMP-1 expression levels and AI are useful prognostic indicators in advanced colorectal carcinoma and suggest that markers of MMP expression might be used in identifying patients who would benefit from new treatment modalities involving MMP inhibitors.
Bendardaf
R
R
Department of Oncology and Radiotherapy, Turku University Central Hospital, Turku, Finland. riyben@utu.fi
Lamlum
H
H
Vihinen
P
P
Ristamäki
R
R
Laine
J
J
Pyrhönen
S
S
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D017364:Collagenases / Q000032:analysis; D015179:Colorectal Neoplasms / Q000201:enzymology*; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000032:analysis*; D053509:Matrix Metalloproteinase 13; D053504:Matrix Metalloproteinases, Membrane-Associated; D008666:Metalloendopeptidases / Q000032:analysis*; D008875:Middle Aged; D016019:Survival Analysis
D014408:Biomarkers, Tumor; D017364:Collagenases; C507079:MMP13 protein, human; D053509:Matrix Metalloproteinase 13; D053504:Matrix Metalloproteinases, Membrane-Associated; D008666:Metalloendopeptidases; D020781:Matrix Metalloproteinase 1