Significance of monocyte chemoattractant protein-1 in angiogenesis and survival in colorectal liver metastases.
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.
Yoshidome
Hiroyuki
H
Department of General Surgery, Chiba University Graduate School of Medicine, Chuo-ku, Chiba 260-8670, Japan. h-yoshidome@faculty.chiba-u.jp
Kohno
Hirohiko
H
Shida
Takashi
T
Kimura
Fumio
F
Shimizu
Hiroaki
H
Ohtsuka
Masayuki
M
Nakatani
Yukio
Y
Miyazaki
Masaru
M
D000368:Aged; D042702:Angiopoietin-2 / Q000096:biosynthesis; D015703:Antigens, CD / Q000096:biosynthesis; D018952:Antigens, CD34 / Q000096:biosynthesis; D015214:Antigens, Differentiation, Myelomonocytic / Q000096:biosynthesis; D018932:Chemokine CCL2 / Q000378:metabolism / Q000502:physiology*; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology*; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology* / Q000556:secondary; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic; D016896:Treatment Outcome; D000097382:CD68 Molecule
D042702:Angiopoietin-2; D015703:Antigens, CD; D018952:Antigens, CD34; D015214:Antigens, Differentiation, Myelomonocytic; D018932:Chemokine CCL2; C067980:CD68 antigen, human; D000097382:CD68 Molecule