Simultaneous measurement of soluble carcinoembryonic antigen and the tissue inhibitor of metalloproteinase TIMP1 serum levels for use as markers of pre-invasive to invasive colorectal cancer

Matrix metalloproteinases (MMP) are members of a multigene family of zinc-d ependent enzymes involved in the degradation of extracellular matrix compon ents. Cancer research suggest that MMP and tissue inhibitors of metalloprot einases (TIMP) may be involved in disease progression; these enzymes could therefore be used as markers in cancer prevention programmes and for clinic al monitoring. To establish whether MMP and TIMP can be used effectively as markers we determined serum levels of MMP1 and TIMP1, and studied the rela tionships between these enzymes and the stage of disease. The potential dia gnostic and prognostic value of serum level measurements of MMP1 and TIMP1 was evaluated by comparing them with serum levels of soluble carcinoembryon ic antigens (sCEA) and p53 antibodies. Our overall results indicate that si multaneous measurements of serum sCEA and TIMP1 in patients with colorectal cancer could be used as prognostic and diagnostic markers for disease prog ression from the pre-invasive nodal phase to the invasive phase (stages I, II to III, IV). In addition, serum levels of TIMP1 could be used as a selec tive marker for metastatic disease (stage III to IV). In fact, the 95% conf idence interval of the serum levels of sCEA at stage III (18.4 less than or equal to sCEA less than or equal to 68.6 ng/ml) and TIMP1 at stage IV (162 0 less than or equal to TIMP1 less than or equal to 3906 ng/ml) identified statistically significant ranges of values (sCEA P = 0.02, TIMP1 P = 0.02), which may be useful in the monitoring of patients at these disease phases. More specifically, our data suggest that, when the serum level of sCEA is below 18.4 ng/ml and the level of TIMP1 below 1690 ng/ml, there is a 95% pr obability that the disease is in the pre-invasive nodal phase: when the ser um level of sCEA falls between 18.4 ng/ml and 68.6 ng/ml and the level of T IMPI is below 1620 ng/ml, there is a 95% probability that the disease is in the phase when lymph node infiltration occurs; when the level of sCEA is a bove 68.6 ng/ml and the level of TIMP1 is at least 1620 ng/ml, there is a 9 5% probability that the disease is in the metastatic phase.