A comparative study of protein expression in primary colorectal cancer and synchronous hepatic metastases: the significance of matrix metalloproteinase-1 expression as a predictor of liver metastasis.
OBJECTIVE
This study was undertaken to determine the ability of protein expression in primary colorectal cancer and metastatic liver tumour tissues to predict hepatic metastasis and intrahepatic recurrence.


METHODS
Sixty patients with colorectal cancer were enrolled in this study. The expression of the following five proteins was assessed by immunohistochemical (IHC) staining: carcinoembryonic antigen (CEA); vascular endothelial growth factor (VEGF); matrix metalloproteinase (MMP)-1; MMP-7; and tissue inhibitor of metalloproteinases (TIMP)-1. Protein expression was measured in patients with primary colorectal cancer without liver metastasis (Group A), in patients with primary colorectal cancer with liver metastasis (primary tumour; Group B), and in patients with resected metastatic liver tumour tissues (liver metastasis; Group C).


RESULTS
IHC staining revealed more protease activity (MMP-1 and -7) in Group B than in Group A. Angiogenic activity (positive VEGF expression) was significantly greater in Group C than in Group B. Multivariate analysis showed that positive MMP-1 expression, the presence of lymphovascular invasion, and an elevated pre-operative serum CEA level (> 5 ng/ml) were significantly related to synchronous liver metastasis. However, intrahepatic recurrence was not related to protein expression, the presence of lymphovascular invasion, or the pre-operative CEA level.


CONCLUSIONS
Our findings suggest that protease activity is important for metastasis, and that angiogenic activity is essential for metastatic tumour growth. Furthermore, positive MMP-1 expression in primary colorectal tumour tissues was a significant predictor of liver metastasis. However, the prognostic impact of protein marker expression in terms of intrahepatic recurrence appears to be minimal.
Kim
Young Wan
YW
Department of Surgery, Yonsei University Health System, Seoul, South Korea.
Ko
Yong Taek
YT
Kim
Nam Kyu
NK
Chung
Hyun Cheol
HC
Min
Byung Soh
BS
Lee
Kang Young
KY
Park
Jong-Pil
JP
Kim
Hoguen
H
D014408:Biomarkers, Tumor / Q000378:metabolism; D002272:Carcinoembryonic Antigen / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism / Q000556:secondary*; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism*; D020783:Matrix Metalloproteinase 7 / Q000378:metabolism; D008875:Middle Aged; D019714:Tissue Inhibitor of Metalloproteinases / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D014408:Biomarkers, Tumor; D002272:Carcinoembryonic Antigen; D019714:Tissue Inhibitor of Metalloproteinases; D042461:Vascular Endothelial Growth Factor A; D020783:Matrix Metalloproteinase 7; D020781:Matrix Metalloproteinase 1