Prognostic and diagnostic implications of MMP-2, MMP-9, and VEGF-α expressions in colorectal cancer.

Purpose: Angiogenesis and tumor invasion are complex processes that are mediated by various proteins, such as vascular endothelial growth factor (VEGF-α) and the matrix-degrading enzymes metalloproteinase-2 and -9 (MMP-2, MMP-9). The aim of this study was to determine what roles MMP-2, MMP-9, and VEGF-α play in colorectal cancer (CRC) by correlating their expression levels with the cancer TNM stage, modified Dukes criteria, degree of cell differentiation, and long-term patient survival.

Methods: The present series consisted of tissue samples obtained from 180 patients who had undergone large bowel resection during 1995 and 2005 at the Luis Antonio Hospital. Archival paraffin-embedded CRC tissue samples were used to generate tissue microarray blocks, which were immunohistochemically stained for MMP-2, MMP-9, and VEGF-α. Three different grading systems were applied to evaluate staining intensity. Chi-squared Person test and Kaplan-Meier survival curves were used, and values of p<0.05 were considered statistically significant.

Results: MMP-2 expression showed a significant association with more invasive cancer stages (p<0.001) and death (p<0.041). VEGF-α expression correlated with a high TNM stage (p<0.009), the degree of cell differentiation (p<0.025) and patient death as a result of disease (p<0.035). The Kaplan-Meier survival estimated that patients with strong staining for MMP-2 (log-rank x(2)=34.09; p<0.0001), MMP-9 (log-rank x(2)=12.83; p<0.0003) and VEGF (log-rank x(2)=33.9; p<0.0001) showed a greater tendency towards death during 60 months of follow up.

Conclusions: The quantification of VEGF-α, MMP-2 and MMP-9 expression in colorectal cancer may be related to survival. These data add to the growing epidemiological and experimental evidence that VEGF-α, MMP-2 and MMP-9 may play a role in colorectal tumorigenesis.