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

Abstract

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.