Expression of Cyclooxygenase-2 in Human Breast Cancer: Relationship with HER-2/neu and other Clinicopathological Prognostic Factors
2
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
Purpose: Previous epidemiologic studies have demonstrated that nonsteroidal anti-inflammatory drugs can reduce the risk of breast cancer, and this possibly happens via cyclooxygenase (COX) inhibition. Moreover, growth factor-inducible COX-2, which is overexpressed in neoplastic tissue, is an attractive therapeutic target. Thus, we evaluated the expression of COX-2 in breast cancer tissues, and we assessed the association between COX-2 expression and HER-2/neu expression and also with several clinicopathological features. Materials and Methods: We analyzed the surgical specimens from 112 women with breast cancer who had undergone lumpectomy or mastectomy. The expressions of COX-2, HER-2/neu, MMP-2 and TIMP-2 were determined immunohistochemically. The correlations between COX-2 expression and several variables, including clinicopathological factors, HER-2/neu expression, MMP-2 expression and TIMP-2 expression were analyzed. Survival analysis was also performed with respect to COX-2 overexpression. Results: The overexpression of COX-2 protein was observed in 28.6% of the breast cancer tissues. Tumors with lymph node metastasis more frequently showed COX-2 overexpression than did those tumors without metastasis (p=0.039), and the increased COX-2 expression correlated positively with HER-2/neu overexpression (p=0.000). No significant differences were found for the MMP-2 or TIMP-2 expression rates in the COX-2 positive and negative groups. The survival analysis revealed no significant differences according to the COX-2 expression. Conclusion: This study results suggest that increased COX-2 expression is related with the progression of breast cancer, e.g., with lymph node invasion. COX-2 overexpression found to be related with HER-2/neu overexpression, but not with MMP-2 or TIMP-2 expression. These results support the potential use of selective agents that inhibit COX-2 or HER-2/neu for the management of breast cancer
Abstract
Purpose: Previous epidemiologic studies have demonstrated that nonsteroidal anti-inflammatory drugs can reduce the risk of breast cancer, and this possibly happens via cyclooxygenase (COX) inhibition. Moreover, growth factor-inducible COX-2, which is overexpressed in neoplastic tissue, is an attractive therapeutic target. Thus, we evaluated the expression of COX-2 in breast cancer tissues, and we assessed the association between COX-2 expression and HER-2/neu expression and also with several clinicopathological features. Materials and Methods: We analyzed the surgical specimens from 112 women with breast cancer who had undergone lumpectomy or mastectomy. The expressions of COX-2, HER-2/neu, MMP-2 and TIMP-2 were determined immunohistochemically. The correlations between COX-2 expression and several variables, including clinicopathological factors, HER-2/neu expression, MMP-2 expression and TIMP-2 expression were analyzed. Survival analysis was also performed with respect to COX-2 overexpression. Results: The overexpression of COX-2 protein was observed in 28.6% of the breast cancer tissues. Tumors with lymph node metastasis more frequently showed COX-2 overexpression than did those tumors without metastasis (p=0.039), and the increased COX-2 expression correlated positively with HER-2/neu overexpression (p=0.000). No significant differences were found for the MMP-2 or TIMP-2 expression rates in the COX-2 positive and negative groups. The survival analysis revealed no significant differences according to the COX-2 expression. Conclusion: This study results suggest that increased COX-2 expression is related with the progression of breast cancer, e.g., with lymph node invasion. COX-2 overexpression found to be related with HER-2/neu overexpression, but not with MMP-2 or TIMP-2 expression. These results support the potential use of selective agents that inhibit COX-2 or HER-2/neu for the management of breast cancer
참고문헌 (24)
- "Aspirin use and reduced risk of fatal colon cancer", 325, pp.1593~6 (1991)
- "Breast cancer and NSAID use:a meta-analysis", 84, pp.1188~92 (2001)
- "Cyclooxygenase-2: a novel target for cancer chemotherapy?", 127, pp.411~7 (2001)
- "COX-2 is expressed in human pulmonary,colonic,and mammary tumors", 89, pp.2637~45 (2000)
- "Expression of cyclooxygenase-2 in human breast carcinoma relevance to tumor angiogenesis and expression of estrogen receptor", pp.286~95 (2001)
- "Prognostic significance of elevated cyclooxy-genase-2 expression in breast cancer", 62, pp.632~5 (2002)
- "Cyclooxygenase-2 expression in human breast cancers and adjacent ductal carcinoma in situ", 62, pp.1676~81 (2002)
- "Cyclo-oxygenase 2 expression is associated with angiogenesis and lymph node metastasis in human breast cancer", 55, pp.429~34 (2002)
- "Clinical value of cyclooxygenase-2 expression in human breast carcinoma", 36, pp.192~8 (2004)
- "Overexpression of cyclooxygenase-2 is sufficient to induce tumorigenesis in transgenic mice", 276(18563-9.) (2001)
- "Increased cyclooxy-genase-2 (COX-2) expression and activity in a murine model of metastatic breast cancer", 93, pp.681~6 (2001)
- "Chemo-prevention of breast cancer in rats by celecoxib, a cyclooxy-genase 2 inhibitor.", 60, pp.2101~3 (2000)
- "Selective cyclooxygenase (COX)-1 or COX-2 inhibitors control metastatic disease in a murine model of breast cancer", 62, pp.2343~6 (2002)
- "Chemopreventive effects of NSAIDs against colo-rectal cancer regulation of apoptosis and mitosis by COX-1 and COX-2", 13, pp.591~7 (1998)
- "Antiangiogenic and antitumor activities of cyclooxygenase-2 inhibitors", 60, pp.1306~11 (2000)
- "Cyclooxygenase-2 expres-sion in human colon cancer cells increases metastatic potential", 94, pp.3336~40 (1997)
- "Activation of matrix metalloproteinase-2 in human breast cancer cells overexpressing cyclooxygenase-1 or -2.", 460, pp.145~8 (1999)
- "Regulation of cyclooxygenase-2 pathway by HER2 receptor", 18, pp.305~14 (1999)
- "Cyclo-oxygenase-2 is overexpressed in HER-2", neu-positive breast cancer evidence for involvement of AP-1 and PEA3, 200218649-57, ~
- "Celecoxib, a selective cyclooxygenase 2 inhibi-tor, protects against human epidermal growth factor receptor 2 (HER-2)", neu-induced breast cancer, 2002, pp.62, 5405~7
- "AJCC cancer staging manual. 5th ed.,", pp.171~80 (1997), Lipincott-Raven
- "Assessment of histological grade. In: Els-ton CW, Ellis IO, eds.", 13, pp.368~76 (1998), Churchill Livingstone
- "Targeting cyclooxygenase 2 and HER-2", neupathways inhibits colorectal carcinoma growth, 2001, pp.120, 1713~9
- "Her-2", neu analysis in archival tissue samplesof human breast cancer:comparison of immunohistochemistryand fluorescence in situ hybridization, 2001, pp.19, 354~63