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


CONCLUSIONS
The preoperative plasma proMMP-2, -9 and TIMP-1 levels have no potential value as diagnostic or prognostic markers in CRC liver metastatic disease.
Waas
E T
ET
Department of Surgery, Radboud University Nijmegen Medical Centre, 6500 HB Nijmegen, The Netherlands.
Wobbes
Th
T
Ruers
T
T
Lomme
R M L M
RM
Hendriks
T
T
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood; D002272:Carcinoembryonic Antigen / Q000097:blood; D015179:Colorectal Neoplasms / Q000097:blood* / Q000401:mortality / Q000473:pathology*; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000097:blood* / Q000401:mortality / Q000556:secondary* / Q000601:surgery; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000097:blood*; D020780:Matrix Metalloproteinase 9 / Q000097:blood*; D008875:Middle Aged; D012680:Sensitivity and Specificity; D015996:Survival Rate; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood*
D014408:Biomarkers, Tumor; D002272:Carcinoembryonic Antigen; D019715:Tissue Inhibitor of Metalloproteinase-1; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9