Effect of the Expression of Matrix Metalloproteases and Their Tissue Inhibitors on Survival of Patients with Resectable Colorectal Cancer

Matrix metalloproteases (MMPs) and their tissue inhibitors (TIMPs) are of crucial importance in the degradation of the stromal connective tissue and basement membrane components. Study of the behavior of these components might help to predict the aggressiveness of tumors. To evaluate the expression and clinical relevance of MMPs and TIMPs for patients with resectable colorectal carcinoma. An immunohistochemical study was performed using tissue arrays and specific antibodies against MMPs-1, 2, 7, 9, 11, 13, and 14, and TIMPs-1, 2 and 3. Determinations were performed in cancer specimens from 104 patients with resectable colorectal cancer. The minimum period of follow-up was 12.5 years for patients without recurrence. To identify specific groups of tumors with distinct expression profiles, the data were analyzed by unsupervised hierarchical cluster analysis. Expression of MMP-11 by fibroblasts and MMP-13 by tumor cells were associated with poor prognosis. The dendrogram revealed first-order division of tumors into two distinct MMP/TIMP molecular profiles, designated group 1 (n = 50) and group 2 (n = 54). Group 2 was characterized by significantly higher expression of MMP-1, 11, and 13, and TIMP-3. Our results emphasize the prognostic value of MMP-11 and 13 expression in colorectal cancer.