Clinical Pathological Study On Cyclooxygenase-2 Expression In Invasion And Metastasis Of Breast Cancer

Objective To investigate the expression of cyclooxygenase-2 (COX-2) in normal breast epithelia, epithelial hyperplasia and breast cancer , to analyze its correlations with the parameters indicating tumor invasion and metastasis including vascular endothelial growth factor (VEGF), microvessel density (MVD) values, matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1), so as to understand the roles of COX-2 in malignant transformation of breast epithelium, tumor invasion and metastasis and to evaluate its clinical pathological significance.Methods The expression of COX-2 was examined by immunohistochemical staining S-P method in tissue microarrays constructed with 45 cases of adjacent normal tissues to breast cancer, 14 cases of adjacent usual ductal hyperplasia (UDH) tissues, 7 cases of ductal carcinoma in situ (DCIS) and 67 cases of infiltrating carcinoma. Meanwhile, the expression of VEGF, MMP-9, TIMP-1 was detected in 67 cases of breast cancer and microvessel density values were also counted in infiltrating carcinomas, for which vascular endothelium marker CD34 antigen was used.Results1. The expression of COX-2 in UDH, DCIS and invasive carcinomas was significant higher than that in their adjacent normal tissues (P < 0.01) . The strong positive rate of COX-2 in infiltrating carcinomas was 65.7% and higher than that in UDH (P <0.05) .2. COX-2 expression in infiltrating carcinomas was not correlated with axillary lymph node metastasis, histological grade, TNM stage and tumor size.3. COX-2 expression in infiltrating carcinomas was positively correlated with VEGF, MMP-9, TIMP-1 and MVD values (P < 0.05) .4. VEGF expression in infiltrating carcinomas was positively correlated with MVD. The mean MVD values in infiltrating carcinomas positively expressing VEGF was 1.5-fold that in negative ones (P < 0.05) .5. In infiltrating carcinomas with COX-2 strong expression, the high expression rate of VEGF and the mean MVD values were 2.0-fold and 1.1-fold that of weak expression of COX-2, respectively.6. A positive relationship was found between the expression of MMP-9 and TIMP-1 in infiltrating carcinomas (P<0.05) .7. In cancers of COX-2 strong expression, there was a positive correlation between the expression of TIMP-1 and axillary lymph node metastasis, a positive correlation between the expression of MMP-9 and histological grade, but no correlation between the expression of VEGF, MMP-9 and axillary lymph node metastasis.8. In cancers of COX-2 weak expression, there was a positive correlation between the expression of MMP-9 and axillary lymph node metastasis, a negative correlation between the expression of MMP-9 and histological grade, but no correlation between the expression of VEGF, TIMP-1 and axillary lymph node metastasis, histological grade.Conclusions1. The expression of COX-2 might be an early, frequent event in malignant transformation of the breast epithelium, and may involve in the development of breast cancer.