Clinicopathological assessment and quantitative estimation of the matrix metalloproteinases MMP-2 and MMP-7 and the inhibitors TIMP-1 and TIMP-2 in colorectal carcinoma tissue samples.

BACKGROUND: The matrix metalloproteinases (MMP) are a family of proteolytic enzymes involved in tumor growth and in the process of invasion. The aim of our study was to test the levels of MMP-2, MMP-7, and the MMP inhibitors TIMP-1 and TIMP-2 mRNA in colorectal carcinoma tissue samples with the clinicopathological status of the disease. PATIENTS AND METHODS: Colorectal carcinoma tissue samples were obtained from 38 patients who underwent resection of colorectal carcinoma. The expression levels of mRNA of MMP-2, MMP-7, TIMP-1, TIMP-2 and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) as a housekeeping gene were quantified in these tissue samples using the method of reverse transcription real-time PCR. RESULTS: It was found that the levels of mRNA expression of MMP-2, TIMP-2, MMP-7 and TIMP-1 were significantly higher in tumor tissue samples than in the normal colorectal tissue (p < 0.0020, p < 0.0467, p < 0.0007 and p < 0.0003 respectively). The level of mRNA expression of MMP-2, MMP-7, TIMP-2 and TIMP-1 did not correlate with the stage of the disease, localization of the tumor, metastatic spread or with disease-free survival (DFI). We recorded a statistically significant inverse negative correlation (r = -0.85; p < 0.0001) between the levels of MMP-7 mRNA and TIMP-2 mRNA. Correlations between the values of mRNA MMP-7 vs. TIMP-1, MMP-2 vs. TIMP-2, MMP-2 vs. TIMP-1 and MMP-2 vs. MMP-7 were not statistically significant. CONCLUSION: We found that there were statistically significant differences in the levels of MMP-2, MMP-7, TIMP-1, TIMP-2 mRNA between normal colorectal tissue and tumor tissue, but we did not find any statistically significant correlation between mRNA levels of MMP-2, MMP-7, TIMP-1, TIMP-2 expression and localization of tumor, clinical stage or course of disease. We found an inverse negative statistically significant correlation between mRNA levels of MMP-7 and TIMP-2. On the basis of these results the clinical use of this approach to the determination of a prognosis is ambiguous.

Quantitative estimation of matrix metalloproteinases 2 and 7 (MMP-2, MMP-7) and tissue inhibitors of matrix metalloproteinases 1 and 2 (TIMP-1, TIMP-2) in colorectal carcinoma tissue samples.

BACKGROUND: An essential step in the process of tumor invasion and metastasis involves the degradation of tissue barriers in the extracellular matrix (ECM), particularly in the basal membrane (BM). Matrix metalloproteinases (MMPs) and tissue inhibitors of matrix metalloproteinases (TIMPs), in particular MMP-2, MMP-7, TIMP-1 and TIMP-2, play an important role in the process of ECM and BM degradation in connection with tumor invasion. The aim of our study was to assess the levels of MMP-2, MMP-7, TIMP-1 and TIMP-2 mRNA expression in colorectal carcinoma tissue samples and to correlate them with the stage of the disease. PATIENTS AND METHODS: The study included samples of tumor tissue of 38 patients with colorectal carcinoma and samples of tissue of 11 patients with benign disease. The expression levels of mRNA MMP-2, MMP-7, TIMP-1, TIMP-2 and glyceraldehyde-3-phosphate dehydrogenase (GAPDH), as housekeeping gene, were quantified in tissue samples using the method of reverse transcription real-time PCR. RESULTS: The levels of mRNA expression of MMP-2, MMP-7 and TIMP-1 were significantly higher in tumor tissue samples that in the control tissue (p<0.0005, p<0.0007 and p<0.0004). In addition the presence of mRNA MMP-2, MMP-7, TIMP-1 and TIMP-2 in tumor tissue samples in these parameters was significantly higher than in the control tissue (p<0.003, p<0.0001, p<0.0001 and p<0.05). CONCLUSION: This pilot study demonstrated that a significant difference in the level and in the presence of mRNA MMP-2, MMP-7 and TIMP-1 expressions between tumor colorectal and control colorectal tissues might be helpful for the prognosis of colorectal cancer.