Cancer progression is a complex multi-step process. Two critical steps in tumor growth and invasion: are the proteolytic processing of the extracellular matrix environment, and the angiogenic switch enabling blood supply into the tumor. Matrix metalloproteases (MMPs) are a group of proteolytic enzymes that degrade components of the extracellular matrix and are implicated in tissue remodeling and tumor infiltration, while Tissue inhibitor of metalloproteinases (TIMPs) inhibit activity of the MMP family and preserve stromal integrity, as a consequence, inhibiting tumor migration. More importantly, the recently documented paradoxical functions of TIMPs have not been characterized in these neoplasms. The aims of the current study were to determine whether TIMP-1 and TIMP-2 has any histopathological significance during colorectal adenocarcinoma progression. Accordingly, 35 colorectal adenocarcinoma paraffin embedded sections prepared from Iraqi patients, in addition to their respective resection margins were retrospectively collected from (liver and gastrointestinal hospital)/Baghdad. Based on immunohistochemical staining, it was found that there were a significant increase in the cellular expression of TIMP-1, and TIMP-2 in all of the 35 tumor samples compared to their respective resection margins (p<0.001, and p<0.001 respectively). Keeping in mind this up regulation of TIMP-1, and TIMP-2, was transient and reflect a host responses to the remodeling stimuli to balance the local tissue degradation process. moreover, when these 35 paraffin embedded sections were broken down according to their various histopathplogical variables, both TIMP-1, and TIMP-2, appear to negatively correlated with tumor histopathplogical variables, still only TIMP-2 revealed a significant negative correlation with both tumor stage and lymph node involvement (rs = -0.463, p<0.01; and rs = -0.482, p<0.01, respectively). In conclusion, TIMP-2 are seem to be more interesting clinical tool compared to (TIMP-1) in CRC, since, it was found to have the play maker role during Duke’s stage progression, and L.N involvement, thus they could be used as targets for therapeutic management of patients with primary colorectal adenocarcinoma.
