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

作者：Kim Young Wan; Ko Yong Taek; Kim Nam Kyu^*; Chung Hyun Cheol; Min Byung Soh; Lee Kang Young; Park Jong Pil; Kim Hoguen

来源：Scandinavian Journal of Gastroenterology, 2010, 45(2): 217-225.

DOI：10.3109/00365520903453158

• Colonic neoplasm
• liver metastasis
• protein expression

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. Material and 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.

• 出版日期2010