High variability in MMP2/TIMP2 and MMP9/TIMP1 expression in secondary liver tumors

The assessment of MMPs/TIMPs expression in various primary tumors has potential prognostic values. Considering the paucity of studies in secondary liver tumors, our aim was to study the expression of MMP2, MMP9, TIMP1, and TIMP2 in secondary hepatic cancer, focusing on their variability in the malignant cells. The study group included 25 cases of liver metastases of colorectal cancer, diagnosed and surgically treated at "Sf. Spiridon" University Hospital of Iassy, Romania. Immunohistochemistry for MMP2, MMP9, TIMP1, and TIMP2 has been performed, followed by the semi-quantitative assessment of the markers using a scoring system based on the positive tumoral cells percentage and the staining intensity. The expression of investigated markers revealed an increased staining variability. The scores showed that MMP2/TIMP2 and MMP9/TIMP1 immunoreactivity was extremely heterogeneous within the analyzed group, with a dominant weak expression for MMP2 and MMP9, in contrast to strong TIMP2 and TIMP1 expression. Ten different patterns of expression of the investigated markers have been identified. No major differences between the expression of MMP2 (14 positive cases) and MMP9 (16 positive cases) could be detected. Our results sustain the inverse correlation between MMP and the correspondent TIMP expression, supporting the hypothesis that MMPs/TIMPs balance has mainly an inhibitory effect on invasiveness. Our study demonstrated that tumoral cells are adapted to MMPs:TIMPs production in the liver microenvironment. The lack of significant differences between MMP2 and MMP9 expression shows that the activity of both MMPs is independent, without reciprocal influences.