Significance of monocyte chemoattractant protein-1 in angiogenesis and survival in colorectal liver metastases

Abstract

Monocyte chemoattractant protein-1 (MCP-1) has been demonstrated to play a role in tumor progression. The present study examined the MCP-1 expression of colorectal liver metastases and determined whether MCP-1 is related to tumor progression and is a predictive marker for survival after hepatic resection of colorectal liver metastases. Eighty-seven patients with colorectal liver metastases were evaluated by immunohistochemistry of MCP-1, Angiopoietin-2, CD68, and CD34 for determination of microvessel density. Clinicopatholgical data were also examined. In a separate experiment, immunohistochemistry of MCP-1 was performed to investigate the expression of primary colorectal tumor according to the clinical stage. MCP-1 mRNA expression was determined in colorectal cancer cell lines. Forty-nine patients (56%) showed high expression of MCP-1 of colorectal liver metastases. High MCP-1 expression was related to multiple colorectal liver metastases. When the degree of MCP-1 expression increased, microvessel density count significantly increased compared with low MCP-1 expression. The MCP-1 expression correlated with Angiopoietin-2 expression. MCP-1 expression of the primary colorectal cancer increased as the clinical stage advanced. The increased MCP-1 mRNA expression was observed in cancer cell lines which have high metastasis potency. Univariate analysis demonstrated that the timing of metastases, tumor size, number of metastases, and MCP-1 expression were significant prognostic factors. Multivariate analysis demonstrated that MCP-1 expression was a significant prognostic factor in hepatic disease-free survival. The MCP-1 expression in colorectal liver metastases, at least in part, may be associated with angiogenesis and be a predictive marker for hepatic recurrence after hepatic resection for colorectal liver metastases.