Japanese Journal of Clinical Oncology Advance Access published online on September 10, 2007
Japanese Journal of Clinical Oncology, doi:10.1093/jjco/hym080
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© 2007 Foundation for Promotion of Cancer Research
Correlations between Cyclooxygenase-2 Expression and Angiogenic Factors in Primary Tumors and Liver Metastases in Colorectal Cancer
Department of Surgical Oncology, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan
For reprints and all correspondence: Hiroyuki Uetake, Department of Surgical Oncology, Graduate School, Tokyo Medical and Dental University 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan. E-mail: h-uetake.srg2{at}tmd.ac.jp
Received October 13, 2006; accepted April 28, 2007
Background: Angiogenesis is required for growth and metastasis of colorectal cancer (CRC), and several positive regulators of tumor angiogenesis have been identified. Cyclooxygenase-2 (COX-2), known to be elevated in several human cancers, regulates angiogenesis by inducing angiogenic factors. The aim of this study was to clarify the levels and evaluate the relationships of COX-2, vascular endothelial growth factor A and C, thymidine phosphorylase (TP) and microvascular density (MVD) in paired tissue specimens between primary CRC and corresponding metastatic liver cancer.
Methods: Tissue samples from pairs of primary tumors and corresponding metastatic liver tumors from 44 patients with CRC were immunohistochemically evaluated for COX-2, VEGF-A, VEGF-C, TP and MVD.
Results: The primary and corresponding metastatic liver tumors tended to show concordant immunoreactivity for COX-2 (P = 0.005, rs = 0.428), VEGF-A (P = 0.039, rs = 0.314), TP (P = 0.005, rs = 0.422) and MVD (P = 0.046, rs = 0.304) by Spearman rank test. The rate of COX-2 immunoreactivity was higher in liver metastases than in primary tumors (P = 0.002), while the rate of VEGF-A was higher in primary tumors than in liver metastases (P = 0.0004). The incidence of TP immunoreactivity and the level of MVD did not differ between primary and metastatic liver tumors (P = 0.247; P = 0.229). Significant correlations were found between COX-2 immunoreactivity and VEGF-A immunoreactivity in metastatic liver tumors (P = 0.033) as well as in primary tumors (P = 0.008).
Conclusion: The positive correlations between COX-2, VEGF-A, TP and MVD in primary CRC and liver metastasis as demonstretaed here will help to predict the angiogenic activity of liver metastasis by analyzing primary tumors, allowing for individualized cancer treatment options.
Key Words: primary colorectal cancer • liver metastases • angiogenesis • cyclooxygenase-2