Genetic Patterns of Metalloproteinases and Their Tissular Inhibitors - Clinicopathologic and Prognostic Significance in Colorectal Cancer

Colorectal cancer (CRC) is the third most common cancer in men and second in women. Progression and invasion of colorectal cancer is a multistep process involving multiple interactions between the tumor and the surrounding stroma mediated by many proteins, among them metalloproteinases (MMPs) and tissular inhibitors of metalloproteinases (TIMPs). We aimed to review the correlations between the expression of the MMPs and TIMPs genes and the clinicopathologic variables of the CRC. Levels of MMPs genes expression in colorectal cancer correlate with the depth of invasion, hematogenous and lymphatic metastasis, poor differentiation, Duke's stage and prognosis. Levels of TIMP's genes expression correlate with better prognosis and longer survival. There are also some controversial data explained by the fact that most of the studies addressed one or few MMPs and÷or TIMPs. The methods to assess the variance in gene expression were not always the same. The promoter regions of metalloproteinases present many polymorphisms and all have allele-specific effects on regulation of MMP gene transcription. Numerous studies on the association of these polymorphisms with cancer susceptibility have been carried out. Most of the studies addressed one or two polymorphisms and their implications. A meta-analysis is necessary to confirm significant correlations. The heterogenicity of the MMPs and TIMPs genetic patterns generated by different studies on colorectal cancer does not allow us to have an overall correlation with clinicopathologic variables and the prognosis of the disease. Studies that involve many MMPs, TIMPs polymorphisms and their tissular expression would be more valuable to better assess the role of those enzymes in the progression of the disease and may serve as a starting point for selective therapeutic approaches.