Expressions of Cyclooxygenase-2 and Ki-67 in Invasive Ductal Carcinoma of Breast Tissues and Their Correlation Analysis_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

 WUJi ¹ ,  GUANXiao-qing ¹ , GUShu-cheng ¹ , ZHENGXiang-xin ¹ , SHIXiao-hong ² , JIANGXiao-ling ² , YUANMu ¹ , ZHANGXu-xu ¹

1. Department of Thyroid and Breast Surgery, Suqian People's Hospital of Nanjing Drum-Tower Hospital Group, Suqian 223800, Jiangsu Province, China;
2. Department of Pathology, Suqian People's Hospital of Nanjing Drum-Tower Hospital Group, Suqian 223800, Jiangsu Province, China;

Corresponding author：

GUANXiao-qing, Email: guan_dr@163.com

Keywords：

Cyclooxygenase-2; Ki-67; Invasive ductal carcinoma of breast; Immunohistochemistry

DOI：

10.7507/1007-9424.20140045

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Objective To study the expressions of cyclooxygenase-2(COX-2) and Ki-67 in the invasive ductal carcinoma (IDC) of breast and to analyze its clinical significance. Methods Immunohistochemical SP method was performed to detect the expressions of COX-2 and Ki-67 in 82 cases of IDC of breast and corresponding tumor-adjacent normal breast tissues, and the relationship of these expressions to clinicopathologic characteristics was analyzed. Results ①The positive rates of COX-2 and Ki-67 protein expressions in the IDC of breast tissues were significantly higher than those in the corresponding tumor-adjacent normal breast tissue [COX-2:71.95%(59/82) versus 8.54%(7/82), χ²=68.56, P < 0.001;Ki-67:64.63%(53/82) versus 13.42%(11/82), χ²=45.20, P < 0.001].②The positive rates of COX-2 and Ki-67 protein expressions were positively correlated with TNM staging (COX-2:r_s=0.349, P < 0.05;Ki-67:r_s=0.305, P < 0.05), lymph node metastasis (COX-2:r_s=0.336, P < 0.05;Ki-67:r_s=0.419, P < 0.01), vascular invasion (COX-2:r_s=0.235, P < 0.05;Ki-67:r_s=0.461, P < 0.01), and histological grade (COX-2:r_s=0.434, P < 0.01;Ki-67:r_s=0.378, P < 0.05).The positive rate of Ki-67 protein expression was positively correlated with tumor diameter (r_s=0.365, P < 0.01), but the positive rate of COX-2 protein expression wasn't correlated with it (r_s=0.135, P > 0.05).The positive rates of COX-2 and Ki-67 protein expressions weren't correlated with menstrual status (COX-2:r_s=0.172, P > 0.05;Ki-67:r_s=0.163, P > 0.05).③The positive rate of COX expression was positively correlated with the positive rate of ki-67 expression (r_s=0.475, P < 0.01). Conclusions There are high-expressions of COX-2 and Ki-67 in IDC of breast.COX-2 and Ki-67 are significantly correlated with the clinicopathologic characteristics in IDC of breast.Combined detection of COX-2 and Ki-67 might calculate the biological behaviors of IDC of breast.COX-2 might be a target of molecular targeted therapy to breast cancer.

Citation： WUJi, GUANXiao-qing, GUShu-cheng, ZHENGXiang-xin, SHIXiao-hong, JIANGXiao-ling, YUANMu, ZHANGXu-xu. Expressions of Cyclooxygenase-2 and Ki-67 in Invasive Ductal Carcinoma of Breast Tissues and Their Correlation Analysis. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2014, 21(2): 197-201. doi: 10.7507/1007-9424.20140045 Copy

1.	Jemal A, Bray F, Center MM, et al.Global cancer statistics[J]. CA Cancer J Clin, 2011, 61(2):69-90.
2.	Gigerenzer G, Mata J, Frank R.Public knowledge of benefits of breast and prostate cancer screening in Europe[J].J Natl Cancer Inst, 2009, 101(17):1216-1220.
3.	姜超, 张峰, 王少军, 等.COX-2与HIF-1α在肝癌中的表达与相关性[J].中国普外基础与临床杂志, 2006, 13(2):142-144.
4.	魏学明, 顾国利, 任力, 等.胃癌组织中EGFR、C-erbB-2、VEGF及COX-2的表达及意义[J].中国普外基础与临床杂志, 2009, 16(11):900-905.
5.	Da MX, Wu XT, Wang J, et al.Expression of cyclooxygenase-2 and vascular endothelial growth factor-C correlates with lymph-angiogenesis and lymphatic invasion in human gastric cancer[J].Arch Med Res, 2008, 39(1):92-99.
6.	李玉民, 薛群基, 周彦明, 等.胃癌组织中环氧合酶-2的表达及其意义[J].中国普外基础与临床杂志, 2003, 10(2):137-139.
7.	张宁, 陶凯雄, 王国斌, 等.环氧合酶-2及血管生成素-2在大肠癌中的表达及临床意义[J].中国普外基础与临床杂志, 2006, 13(5):564-567.
8.	Matsubayashi H, Infante JR, Winter J, et al.Tumor COX-2 expression and prognosis of patients with resectable pancreatic cancer[J].Cancer Biol Ther, 2007, 6(10):1569-1575.
9.	陈振栋, 谭浪平, 王亚洲, 等.角质细胞生长因子和环氧化酶-2在胃癌中的表达及其与血管生成的关系[J].中国普外基础与临床杂志, 2011, 18(2):177-182.
10.	祝玉祥, 章佳新, 邵稳喜, 等.ki67在三阴性乳腺癌组织中的表达及意义[J].中国现代普通外科进展, 2010, 13(9):679-680, 697.
11.	Edge SB, Byrd DR, Compton CC, et al.AJCC Cancer Staging Manual[M].7th ed.New York:Springer, 2009:643-648.
12.	杨阳, 钱晓萍, 陈洁宇, 等.COX-2在乳腺癌组织的表达及其与临床病理参数的相关性[J].现代肿瘤医学, 2009, 17(8):1467-1471.
13.	解兰亭, 李进岩, 刘爱东, 等.COX-2和p53在乳腺癌组织中的表达及其临床意义[J].临床外科杂志, 2009, 17(10):693-694.
14.	邹天宁, 胡凤娣, 陈艳, 等.乳腺癌组织Cox-2和ERβmRNA表达及其相关性研究[J].中华肿瘤防治杂志, 2008, 15(10):758-761.
15.	Oliveira VM, Piato S, Silva MA.Correlation of cyclooxygenase-2 and aromatase immunohistochemical expression in invasive ductal carcinoma, ductal carcinoma in situ, and adjacent normal epithelium[J].Breast Cancer Res Treat, 2006, 95(3):235-241.
16.	刘秀静, 刘雨清.COX-2和survivin在乳腺癌组织中的表达及其相关性[J].潍坊医学院学报, 2009, 31(6):462-464.
17.	Chell S, Kaidi A, Kadi A, et al.Mediators of PGE2 synthesis and signalling downstream of COX-2 represent potential targets for the prevention/treatment of colorectal cancer[J].Biochim Biophys Acta, 2006, 1766(1):104-119.
18.	郭贵龙, 杨光伦, 李卓英, 等.环氧合酶-2对乳腺癌淋巴管形成的影响[J].中华外科杂志, 2008, 46(2):132-135.
19.	Singh B, Cook KR, Vincent L, et al.Cyclooxygenase-2 induces genomic instability, BCL2 expression, doxorubicin resistance, and altered cancer-initiating cell phenotype in MCF7 breast cancer cells[J].J Surg Res, 2008, 147(2):240-246.
20.	Gerdes J, Schwab U, Lemke H, et al.Production of a mouse monoclonal antibody reactive with a human nuclear antigen associate with cell proliferation[J].Int J Cancer, 1983, 31(1):13-20.
21.	杨雪琴, 李雁.Ki67在乳腺癌的研究进展[J].武汉大学学报:医学版, 2011, 32(6):852-856.
22.	钱金锋, 谢慧君, 蔡德巍, 等.Her2和Ki-67在乳腺癌中的表达和意义[J].交通医学, 2011, 25(1):28-30.
23.	Yerushalmi R, Woods R, Ravdin PM, et al.Ki67 in breast cancer:prognostic and predictive potential[J].Lancet Oncol, 2010, 11(2):174-183.
24.	Santisteban M, Reynolds C, Barr Fritcher EG, et al.Ki67:a time-varying biomarker of risk of breast cancer in atypical hyperplasia[J].Breast Cancer Res Treat, 2010, 121(2):431-437.
25.	von Minckwitz G, Sinn HP, Raab G, et al.Clinical response after two cycles compared to HER2, Ki-67, p53, and bcl-2 in independently predicting a pathological complete response after preoperative chemotherapy in patients with operable carcinoma of the breast[J].Breast Cancer Res, 2008, 10(2):R30.
26.	管小青, 吴骥, 顾书成, 等.survivin与p53、Ki67在复发转移性乳腺癌组织中表达及相关性研究[J].中国普外基础与临床杂志, 2011, 18(3):290-294.
27.	谢春华, 杨基鹏, 刘峥, 等.Ki67、VEGF、nm²3在乳腺癌组织中表达的相关性及临床意义[J].中国肿瘤外科杂志, 2011, 3(6):325-328.
28.	Klintman M, Bendahl PO, Grabau D, et al.The prognostic value of Ki67 is dependent on estrogen receptor status and histological grade in premenopausal patients with node-negative breast cancer[J].Mod Pathol, 2010, 23(2):251-259.

1. Jemal A, Bray F, Center MM, et al.Global cancer statistics[J]. CA Cancer J Clin, 2011, 61(2):69-90.
2. Gigerenzer G, Mata J, Frank R.Public knowledge of benefits of breast and prostate cancer screening in Europe[J].J Natl Cancer Inst, 2009, 101(17):1216-1220.
3. 姜超, 张峰, 王少军, 等.COX-2与HIF-1α在肝癌中的表达与相关性[J].中国普外基础与临床杂志, 2006, 13(2):142-144.
4. 魏学明, 顾国利, 任力, 等.胃癌组织中EGFR、C-erbB-2、VEGF及COX-2的表达及意义[J].中国普外基础与临床杂志, 2009, 16(11):900-905.
5. Da MX, Wu XT, Wang J, et al.Expression of cyclooxygenase-2 and vascular endothelial growth factor-C correlates with lymph-angiogenesis and lymphatic invasion in human gastric cancer[J].Arch Med Res, 2008, 39(1):92-99.
6. 李玉民, 薛群基, 周彦明, 等.胃癌组织中环氧合酶-2的表达及其意义[J].中国普外基础与临床杂志, 2003, 10(2):137-139.
7. 张宁, 陶凯雄, 王国斌, 等.环氧合酶-2及血管生成素-2在大肠癌中的表达及临床意义[J].中国普外基础与临床杂志, 2006, 13(5):564-567.
8. Matsubayashi H, Infante JR, Winter J, et al.Tumor COX-2 expression and prognosis of patients with resectable pancreatic cancer[J].Cancer Biol Ther, 2007, 6(10):1569-1575.
9. 陈振栋, 谭浪平, 王亚洲, 等.角质细胞生长因子和环氧化酶-2在胃癌中的表达及其与血管生成的关系[J].中国普外基础与临床杂志, 2011, 18(2):177-182.
10. 祝玉祥, 章佳新, 邵稳喜, 等.ki67在三阴性乳腺癌组织中的表达及意义[J].中国现代普通外科进展, 2010, 13(9):679-680, 697.
11. Edge SB, Byrd DR, Compton CC, et al.AJCC Cancer Staging Manual[M].7th ed.New York:Springer, 2009:643-648.
12. 杨阳, 钱晓萍, 陈洁宇, 等.COX-2在乳腺癌组织的表达及其与临床病理参数的相关性[J].现代肿瘤医学, 2009, 17(8):1467-1471.
13. 解兰亭, 李进岩, 刘爱东, 等.COX-2和p53在乳腺癌组织中的表达及其临床意义[J].临床外科杂志, 2009, 17(10):693-694.
14. 邹天宁, 胡凤娣, 陈艳, 等.乳腺癌组织Cox-2和ERβmRNA表达及其相关性研究[J].中华肿瘤防治杂志, 2008, 15(10):758-761.
15. Oliveira VM, Piato S, Silva MA.Correlation of cyclooxygenase-2 and aromatase immunohistochemical expression in invasive ductal carcinoma, ductal carcinoma in situ, and adjacent normal epithelium[J].Breast Cancer Res Treat, 2006, 95(3):235-241.
16. 刘秀静, 刘雨清.COX-2和survivin在乳腺癌组织中的表达及其相关性[J].潍坊医学院学报, 2009, 31(6):462-464.
17. Chell S, Kaidi A, Kadi A, et al.Mediators of PGE2 synthesis and signalling downstream of COX-2 represent potential targets for the prevention/treatment of colorectal cancer[J].Biochim Biophys Acta, 2006, 1766(1):104-119.
18. 郭贵龙, 杨光伦, 李卓英, 等.环氧合酶-2对乳腺癌淋巴管形成的影响[J].中华外科杂志, 2008, 46(2):132-135.
19. Singh B, Cook KR, Vincent L, et al.Cyclooxygenase-2 induces genomic instability, BCL2 expression, doxorubicin resistance, and altered cancer-initiating cell phenotype in MCF7 breast cancer cells[J].J Surg Res, 2008, 147(2):240-246.
20. Gerdes J, Schwab U, Lemke H, et al.Production of a mouse monoclonal antibody reactive with a human nuclear antigen associate with cell proliferation[J].Int J Cancer, 1983, 31(1):13-20.
21. 杨雪琴, 李雁.Ki67在乳腺癌的研究进展[J].武汉大学学报:医学版, 2011, 32(6):852-856.
22. 钱金锋, 谢慧君, 蔡德巍, 等.Her2和Ki-67在乳腺癌中的表达和意义[J].交通医学, 2011, 25(1):28-30.
23. Yerushalmi R, Woods R, Ravdin PM, et al.Ki67 in breast cancer:prognostic and predictive potential[J].Lancet Oncol, 2010, 11(2):174-183.
24. Santisteban M, Reynolds C, Barr Fritcher EG, et al.Ki67:a time-varying biomarker of risk of breast cancer in atypical hyperplasia[J].Breast Cancer Res Treat, 2010, 121(2):431-437.
25. von Minckwitz G, Sinn HP, Raab G, et al.Clinical response after two cycles compared to HER2, Ki-67, p53, and bcl-2 in independently predicting a pathological complete response after preoperative chemotherapy in patients with operable carcinoma of the breast[J].Breast Cancer Res, 2008, 10(2):R30.
26. 管小青, 吴骥, 顾书成, 等.survivin与p53、Ki67在复发转移性乳腺癌组织中表达及相关性研究[J].中国普外基础与临床杂志, 2011, 18(3):290-294.
27. 谢春华, 杨基鹏, 刘峥, 等.Ki67、VEGF、nm²3在乳腺癌组织中表达的相关性及临床意义[J].中国肿瘤外科杂志, 2011, 3(6):325-328.
28. Klintman M, Bendahl PO, Grabau D, et al.The prognostic value of Ki67 is dependent on estrogen receptor status and histological grade in premenopausal patients with node-negative breast cancer[J].Mod Pathol, 2010, 23(2):251-259.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Expressions of Cyclooxygenase-2 and Ki-67 in Invasive Ductal Carcinoma of Breast Tissues and Their Correlation Analysis

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