Matrix metalloproteinase/tissue inhibitors of matrix metalloproteinase phenotype identifies poor prognosis colorectal cancers.
OBJECTIVE
The matrix metalloproteinases (MMPs) are a family of proteolytic enzymes involved in tumor invasion; several individual members of which have been implicated in tumor prognosis. These enzymes and their physiologic inhibitors, the tissue inhibitors of matrix metalloproteinases (TIMPs), act in a coordinated manner to form an integrated system. Therefore, to understand their role in tumor invasion, it is necessary to evaluate them collectively.


METHODS
In this study all of the major members of the matrix metalloproteinase (MMP-1, MMP-2, MMP-3, MMP-7, MMP-9, MMP-13, MT1-MMP and MT2-MMP)/tissue inhibitor of matrix metalloproteinase (TIMP-1, TIMP-2, and TIMP-3) system have been investigated by immunohistochemistry in a series (n = 90) of stage III (Dukes' C) colorectal cancers. An immunohistochemical score based on the intensity of immunoreactivity and proportion of immunoreactive cells was established for each MMP and TIMP.


RESULTS
The MMP/TIMP profile defined by hierarchical cluster analysis of the immunohistochemical score identifies a distinct group of colorectal cancers with poor prognosis (log-rank test, 12.22, P = 0.0005). The median survival time of patients in this survival group was 18 months compared with a median survival of 49 months in the "good" survival group. Multivariate analysis showed that this profile was independently the most significant prognostic factor (P = 0.001).


CONCLUSIONS
This study has identified that the MMP/TIMP profile is an independent indicator of poor prognosis in colorectal cancer.
Curran
Stephanie
S
Department of Pathology, University of Aberdeen, Aberdeen, United Kingdom. s.curran@abdn.ac.uk
Dundas
Sinclair R
SR
Buxton
Jenny
J
Leeman
Matthew F
MF
Ramsay
Robin
R
Murray
Graeme I
GI
D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008207:Lymphatic Metastasis / Q000473:pathology; D008297:Male; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D010641:Phenotype; D011379:Prognosis; D015996:Survival Rate; D019714:Tissue Inhibitor of Metalloproteinases / Q000378:metabolism*
D014408:Biomarkers, Tumor; D019714:Tissue Inhibitor of Metalloproteinases; D020782:Matrix Metalloproteinases