Circulating gelatinases and tissue inhibitor of metalloproteinase-1 in colorectal cancer metastatic liver disease

Abstract

Aims The degradation of the extracellular matrix is intrinsic to the invasion and progression of cancer. Matrix metalloproteinase (MMP)-2 and -9 and their natural inhibitors are involved in this process. The study aims to investigate if plasma MMP-2, -9 and tissue inhibitor of metalloproteinase-1 (TIMP-1) can be useful markers in the diagnosis and prognosis of colorectal cancer (CRC) metastatic liver disease. Methods Fifty-seven patients undergoing liver metastasis operation were followed prospectively. ProMMP-2, -9 and TIMP-1 plasma levels were determined by zymography and ELISA, before and after the resection of liver metastases. Data were compared with those of healthy controls ( n = 51) and primary CRC patients ( n = 94). The diagnostic and prognostic potential was investigated with ROC-curves and Kaplan–Meier survival analysis. Results Plasma proMMP-2 levels were lower ( P < 0.001), and TIMP-1 levels higher ( P < 0.001) in CRC metastatic liver disease than in healthy controls. If compared to those in primary CRC patients, no differences were found. In ROC-curves, the area under the curve was 0.48 and 0.61 for proMMP-2 and -9, respectively. Plasma proMMP-2, -9 and TIMP-1 levels were unsuitable to predict survival. In both diagnostic and prognostic examinations, CEA proved to be a better marker. In the postoperative follow-up, protracted low levels of proMMP-2 seemed related to disease recurrence. Conclusion The preoperative plasma proMMP-2, -9 and TIMP-1 levels have no potential value as diagnostic or prognostic markers in CRC liver metastatic disease.