Correlative Research of Ki-67 Antigen in Breast Cancer_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

 SUNLi-ting ,  GUOLi-ying

Department of Breast Surgery, The First Affiliated Hospital, Xinjiang Medical University, Urumqi 830054, Xinjiang uyghur autonomous region, China;

Corresponding author：

GUOLi-ying, Email: ggs318@126.com

Keywords：

Ki-67 antigen; Breast cancer; Cell proliferation; Clinical application

DOI：

10.7507/1007-9424.20140157

Video：

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Objective To explore the expression of Ki-67 antigen in the breast cancer tissues and to evaluate the relationship of the expression to biology behavior as well as prognosis of breast cancer. Method Literatures about relation between Ki-67 and breast cancer were reviewed. Results The expression of Ki-67 in the breast cancer tissue was obviously higher than that in the adjacent to cancer tissue or normal breast tissue. The Ki-67 positive expression rate was positively correlated with pathology classification and clinical stage of breast cancer, the correlation was not consistent about the expression of Ki-67 and axillary lymph node metastasis of breast cancer. Conclusions Ki-67 is a cell proliferation nuclear antigen related to cell cycle, and its expression changes along with the change of cell cycle, it has been employed as a reliable marker of cell proliferation. The expression of Ki-67 has an important significance in early diagnosis and guiding of neoadjuvant chemotherapy as well as prognosis of breast cancer.

Citation： SUNLi-ting, GUOLi-ying. Correlative Research of Ki-67 Antigen in Breast Cancer. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2014, 21(5): 650-653. doi: 10.7507/1007-9424.20140157 Copy

1.	Jemal A, Bray F, Center MM, et al.Global cancer statistics[J].CA Cancer J Clin, 2011, 61(2):69-90.
2.	杨桦, 王思愚, 区伟, 等.华南地区年轻乳腺癌患者的临床特征及预后因素分析[J].癌症, 2009, 28(12):1310-1316.
3.	Fredholm H, Eaker S, Frisell J, et al.Breast cancer in young women:Poor survival despite intensive treatment[J].PLoS One, November 11, 2009.doi:10.1371/journal.pone.0007695.
4.	马志君, 吉洁.Ki67与肿瘤关系的研究进展[J].中国医疗前沿, 2012, 7(7):15-17.
5.	邓秀娟, 吴海根.PTEN、Ki67在卵巢恶性肿瘤组织中的研究进展[J].现代肿瘤医学, 2012, 20(10):2182-2184.
6.	Goldhirsch A, Ingle JN, Gelber RD, et al.Thresholds for therapies:highlights of the St Gallen International Expert Consensus on the primary therapy of early breast cancer 2009[J].Ann Oncol, 2009, 20(8):1319-1329.
7.	Oakman C, Bessi S, Zafarana E, et al.Recent advances in systemic therapy.New diagnostics and biological predictors of outcome in early breast cancer[J].Breast Cancer Res, 2009, 11(2):205.
8.	Gerdes J, Schwab U, Lemke H, et al.Production of a mouse monoclonal antibody reactive with a human nuclear antigen associated with cell proliferation[J].Int J Cancer, 1983, 31(1):13-20.
9.	Schlüter C, Duchrow M, Wohlenberg C, et al.The cell proliferation-associated antigen of antibody Ki-67:a very large, ubiquitous nuclear protein with numerous repeated elements, representing a new kind of cell cycle-maintaining proteins[J].J Cell Biol, 1993, 123(3):513-522.
10.	MacCallum DE, Hall PA.The location of pKi67 in the outer dense fibrillary compartment of the nucleolus points to a role in ribosome biogenesis during the cell division cycle[J].J Pathol, 2000, 190(5):537-544.
11.	Rahmanzadeh R, Hüttmann G, Gerdes J, et al.Chromophoreassisted light inactivation of pKi-67 leads to inhibition of ribosomal RNA synthesis[J].Cell Prolif, 2007, 40(3):422-430.
12.	Beresford MJ, Wilson GD, Makris A.Measuring proliferation in breast cancer:practicalities and applications[J].Breast Cancer Res, 2006, 8(6):216.
13.	韩益玲, 陈芳源, 钟璐.Ki67抗原在白血病研究中的应用[J].诊断学理论与实践, 2008, 7(3):348-351.
14.	程广保, 吴璟霞.乳腺癌发病的基因调控机制[J].现代肿瘤医学, 2010, 18(9):1848-1852.
15.	王合兵, 肖坚, 陈文新.ER、PR、p53及HER-2在113例乳腺癌中的表达及临床意义[J].肿瘤学杂志, 2010, 16(9):718-720.
16.	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.
17.	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.
18.	徐玲, 刘荫华, 叶京明, 等.乳腺癌组织Ki67表达与恩环类联合紫杉类新辅助化疗效果的相关性[J].中华外科杂志, 2010, 48(6):450-453.
19.	Cheang MC, Chia SK, Voduc D, et al.Ki67 index, HER2 status, and prognosis of patients with luminal B breast cancer[J].J Natl Cancer Inst, 2009, 101(10):736-750.
20.	Tan PH, Bay BH, Yip G, et al.Immunohistochemical detection of Ki67 in breast cancer correlates with transcriptional regulation of genes related to apoptosis and cell death[J].Mod Pathol, 2005, 18(3):374-381.
21.	俸瑞发, 柏璐, 郑默然, 等.乳腺癌组织HIF-1α、Ki67及VEGF表达的临床意义[J].中华内分泌外科杂志, 2013, 7(2):93-97.
22.	Yerushalmi R, Woods R, Ravdin PM, et al.Ki67 in breast cancer:prognostic and predictive potential[J].Lancet Oncol, 2010, 11(2):174-183.
23.	朴正日, 金全金, 申龙河.Ki67在乳腺癌组织中表达及其与C-erbB-2、ER、PR、P53基因的关系[J].中国民康医学, 2010, 22(3):258-260, 265.
24.	Bhatavdekar JM, Patel DD, Shah NG, et al.Prognostic significance of immunohistochemically localized biomarkers in stageⅡand stageⅢbreast cancer:a multivariate analysis[J].Ann Surg Oncol, 2000, 7(4):305-311.
25.	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.
26.	段倞彦.ki67蛋白在乳腺癌组织中的表达及临床意义[J].中国医药指南, 2013, 1(6):187-188.
27.	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.
28.	贾静, 孟令华.乳腺癌组织中BCSG1和Ki67的表达与临床意义[J].河北医药, 2012, 34(9):1295-1297.
29.	郭彦伟.ki67在乳腺癌组织中的表达及其临床意义[J].中国临床实用医学, 2009, 3(4):97-98.
30.	刘广舒, 高云, 郭鹏, 等.C-erbB-2、Ki67、nm23基因表达与乳腺癌腋窝淋巴结转移的相关性分析[J].实用预防医学, 2013, 20(3):340-342.
31.	王建法, 顾超, 叶宣光.乳腺癌淋巴结转移与Ki67、VEGF表达的相关性及其临床意义[J].实用癌症杂志, 2009, 24(5):450-451.
32.	Goldhirsch A, Wood WC, Coates AS, et al.Strategies for subtypes-dealing with the diversity of breast cancer:highlights of the St.Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2011[J].Ann Oncol, 2011, 22(8):1736-1747.
33.	沈三弟, 陈卓荣, 黄湛, 等.Ki67在不同分子类型乳腺癌组织中的表达及意义[J].实用癌症杂志, 2012, 27(3):247-249.
34.	徐婷, 何奇, 吴克瑾, 等.三阴性乳腺癌中p53和Ki67表达的相关研究[J].上海交通大学学报:医学版, 2013, 33(6):833-837.
35.	Tanei T, Shimomura A, Shimazu K, et al.Prognostic significance of Ki67 index after neoadjuvant chemotherapy in breast cancer[J].Eur J Surg Oncol, 2011, 37(2):155-161.
36.	Lønning PE.Poor-prognosis estrogen receptor-positive disease:present and future clinical solutions[J].Ther Adv Med Oncol, 2012, 4(3):127-137.
37.	张同先, 王亚红, 张巍, 等.Ki67作为ER+和(或) PR+乳腺癌进一步分型指标的研究[J].实用医学杂志, 2013, 29(3):374-377.
38.	张好云, 陈天文, 王开昕, 等.Ki67表达在乳腺癌新辅助化疗中的临床意义[J].实用医院临床杂志, 2012, 9(4):60-62.
39.	Kontzoglou K, Palla V, Karaolanis G, et al.Correlation between Ki67 and breast cancer prognosis[J].Oncology, 2013, 84(4):219-225.
40.	肖宇, 李惠平, 雷玉涛, 等.乳腺癌新辅助化疗疗效及ER/PR, HER2, Ki67, CyclinA2的化疗预测作用[J].中国微创外科杂志, 2011, 11(2):163-167.
41.	韦祝新, 王绍丰.恶性肿瘤生物特性与Ki67基因表达的关系研究进展[J].中国医药导刊, 2011, 13(8):1388-1389.

1. Jemal A, Bray F, Center MM, et al.Global cancer statistics[J].CA Cancer J Clin, 2011, 61(2):69-90.
2. 杨桦, 王思愚, 区伟, 等.华南地区年轻乳腺癌患者的临床特征及预后因素分析[J].癌症, 2009, 28(12):1310-1316.
3. Fredholm H, Eaker S, Frisell J, et al.Breast cancer in young women:Poor survival despite intensive treatment[J].PLoS One, November 11, 2009.doi:10.1371/journal.pone.0007695.
4. 马志君, 吉洁.Ki67与肿瘤关系的研究进展[J].中国医疗前沿, 2012, 7(7):15-17.
5. 邓秀娟, 吴海根.PTEN、Ki67在卵巢恶性肿瘤组织中的研究进展[J].现代肿瘤医学, 2012, 20(10):2182-2184.
6. Goldhirsch A, Ingle JN, Gelber RD, et al.Thresholds for therapies:highlights of the St Gallen International Expert Consensus on the primary therapy of early breast cancer 2009[J].Ann Oncol, 2009, 20(8):1319-1329.
7. Oakman C, Bessi S, Zafarana E, et al.Recent advances in systemic therapy.New diagnostics and biological predictors of outcome in early breast cancer[J].Breast Cancer Res, 2009, 11(2):205.
8. Gerdes J, Schwab U, Lemke H, et al.Production of a mouse monoclonal antibody reactive with a human nuclear antigen associated with cell proliferation[J].Int J Cancer, 1983, 31(1):13-20.
9. Schlüter C, Duchrow M, Wohlenberg C, et al.The cell proliferation-associated antigen of antibody Ki-67:a very large, ubiquitous nuclear protein with numerous repeated elements, representing a new kind of cell cycle-maintaining proteins[J].J Cell Biol, 1993, 123(3):513-522.
10. MacCallum DE, Hall PA.The location of pKi67 in the outer dense fibrillary compartment of the nucleolus points to a role in ribosome biogenesis during the cell division cycle[J].J Pathol, 2000, 190(5):537-544.
11. Rahmanzadeh R, Hüttmann G, Gerdes J, et al.Chromophoreassisted light inactivation of pKi-67 leads to inhibition of ribosomal RNA synthesis[J].Cell Prolif, 2007, 40(3):422-430.
12. Beresford MJ, Wilson GD, Makris A.Measuring proliferation in breast cancer:practicalities and applications[J].Breast Cancer Res, 2006, 8(6):216.
13. 韩益玲, 陈芳源, 钟璐.Ki67抗原在白血病研究中的应用[J].诊断学理论与实践, 2008, 7(3):348-351.
14. 程广保, 吴璟霞.乳腺癌发病的基因调控机制[J].现代肿瘤医学, 2010, 18(9):1848-1852.
15. 王合兵, 肖坚, 陈文新.ER、PR、p53及HER-2在113例乳腺癌中的表达及临床意义[J].肿瘤学杂志, 2010, 16(9):718-720.
16. 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.
17. 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.
18. 徐玲, 刘荫华, 叶京明, 等.乳腺癌组织Ki67表达与恩环类联合紫杉类新辅助化疗效果的相关性[J].中华外科杂志, 2010, 48(6):450-453.
19. Cheang MC, Chia SK, Voduc D, et al.Ki67 index, HER2 status, and prognosis of patients with luminal B breast cancer[J].J Natl Cancer Inst, 2009, 101(10):736-750.
20. Tan PH, Bay BH, Yip G, et al.Immunohistochemical detection of Ki67 in breast cancer correlates with transcriptional regulation of genes related to apoptosis and cell death[J].Mod Pathol, 2005, 18(3):374-381.
21. 俸瑞发, 柏璐, 郑默然, 等.乳腺癌组织HIF-1α、Ki67及VEGF表达的临床意义[J].中华内分泌外科杂志, 2013, 7(2):93-97.
22. Yerushalmi R, Woods R, Ravdin PM, et al.Ki67 in breast cancer:prognostic and predictive potential[J].Lancet Oncol, 2010, 11(2):174-183.
23. 朴正日, 金全金, 申龙河.Ki67在乳腺癌组织中表达及其与C-erbB-2、ER、PR、P53基因的关系[J].中国民康医学, 2010, 22(3):258-260, 265.
24. Bhatavdekar JM, Patel DD, Shah NG, et al.Prognostic significance of immunohistochemically localized biomarkers in stageⅡand stageⅢbreast cancer:a multivariate analysis[J].Ann Surg Oncol, 2000, 7(4):305-311.
25. 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.
26. 段倞彦.ki67蛋白在乳腺癌组织中的表达及临床意义[J].中国医药指南, 2013, 1(6):187-188.
27. 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.
28. 贾静, 孟令华.乳腺癌组织中BCSG1和Ki67的表达与临床意义[J].河北医药, 2012, 34(9):1295-1297.
29. 郭彦伟.ki67在乳腺癌组织中的表达及其临床意义[J].中国临床实用医学, 2009, 3(4):97-98.
30. 刘广舒, 高云, 郭鹏, 等.C-erbB-2、Ki67、nm23基因表达与乳腺癌腋窝淋巴结转移的相关性分析[J].实用预防医学, 2013, 20(3):340-342.
31. 王建法, 顾超, 叶宣光.乳腺癌淋巴结转移与Ki67、VEGF表达的相关性及其临床意义[J].实用癌症杂志, 2009, 24(5):450-451.
32. Goldhirsch A, Wood WC, Coates AS, et al.Strategies for subtypes-dealing with the diversity of breast cancer:highlights of the St.Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2011[J].Ann Oncol, 2011, 22(8):1736-1747.
33. 沈三弟, 陈卓荣, 黄湛, 等.Ki67在不同分子类型乳腺癌组织中的表达及意义[J].实用癌症杂志, 2012, 27(3):247-249.
34. 徐婷, 何奇, 吴克瑾, 等.三阴性乳腺癌中p53和Ki67表达的相关研究[J].上海交通大学学报:医学版, 2013, 33(6):833-837.
35. Tanei T, Shimomura A, Shimazu K, et al.Prognostic significance of Ki67 index after neoadjuvant chemotherapy in breast cancer[J].Eur J Surg Oncol, 2011, 37(2):155-161.
36. Lønning PE.Poor-prognosis estrogen receptor-positive disease:present and future clinical solutions[J].Ther Adv Med Oncol, 2012, 4(3):127-137.
37. 张同先, 王亚红, 张巍, 等.Ki67作为ER+和(或) PR+乳腺癌进一步分型指标的研究[J].实用医学杂志, 2013, 29(3):374-377.
38. 张好云, 陈天文, 王开昕, 等.Ki67表达在乳腺癌新辅助化疗中的临床意义[J].实用医院临床杂志, 2012, 9(4):60-62.
39. Kontzoglou K, Palla V, Karaolanis G, et al.Correlation between Ki67 and breast cancer prognosis[J].Oncology, 2013, 84(4):219-225.
40. 肖宇, 李惠平, 雷玉涛, 等.乳腺癌新辅助化疗疗效及ER/PR, HER2, Ki67, CyclinA2的化疗预测作用[J].中国微创外科杂志, 2011, 11(2):163-167.
41. 韦祝新, 王绍丰.恶性肿瘤生物特性与Ki67基因表达的关系研究进展[J].中国医药导刊, 2011, 13(8):1388-1389.

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Correlative Research of Ki-67 Antigen in Breast Cancer

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