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AIM: To clarify the clinicopathologic significance of COX-2expression in human colorectal cancer.METHODS: A total of 128 surgically resected colorectal cancer specimens were immunohistochemically analyzed with the use of anti-COX-2, anti-VEGF and antiMMP-2 antibodies. The relationship between the cyclooxygenase-2 expression in primary lesions of colorectal cancer and clinicopathologic parameters was evaluated by chi-square test.RESULTS: Among 128 cases of colorectal cancer, 87(67.9%) were positive for cyclooxygenase-2. The expression of cyclooxygenase-2 was significantly correlated with the depth of invasion, stage of disease,and metastasis (lymph node and liver). Patients in T3-T4,stages Ⅲ-Ⅳ and with metastasis had much higher expression of cyclooxygenase-2 than ones in T1-T2, stages Ⅰ-Ⅱ and without metastasis (P＜0.05). Among 45 cases of colorectal cancer with lymph node metastasis, the COX-2-positive rate was 86.7% (39/45) for primary lesions and diffuse cytoplasmic staining for COX-2 protein was detected in cancer cells in 100% of metastatic lesions of the lymph nodes. VEGF expression was detected in 49tumors (38.3%), and VEGF expression was closely correlated with COX-2 expression. The positive expression rate of VEGF (81.6%) in the cyclooxygenase-2-positive group was higher than that in the cyclooxygenase-2-negative group (18.4%, P＜0.05). MMP-2 expression was detected in 88 tumors (68.8%), and MMP-2 expression was closely correlated with COX-2 expression. The positive expression rate of MMP-2 (79.6%) in the positive COX-2group was higher than that in the negative COX-2 group (20.4%, P＜0.05).CONCLUSION: Cyclooxygenase-2 may be associated with tumor progression by modulating the angiogenesis and cancer cell motility and invasive potential in colorectal cancer and it can be used as a possible biomarker.