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.	楊樺, 王思愚, 區偉, 等.華南地區年輕乳腺癌患者的臨床特征及預后因素分析[J].癌癥, 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.	馬志君, 吉潔.Ki67與腫瘤關系的研究進展[J].中國醫療前沿, 2012, 7(7):15-17.
5.	鄧秀娟, 吳海根.PTEN、Ki67在卵巢惡性腫瘤組織中的研究進展[J].現代腫瘤醫學, 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.	韓益玲, 陳芳源, 鐘璐.Ki67抗原在白血病研究中的應用[J].診斷學理論與實踐, 2008, 7(3):348-351.
14.	程廣保, 吳璟霞.乳腺癌發病的基因調控機制[J].現代腫瘤醫學, 2010, 18(9):1848-1852.
15.	王合兵, 肖堅, 陳文新.ER、PR、p53及HER-2在113例乳腺癌中的表達及臨床意義[J].腫瘤學雜志, 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.	楊雪琴, 李雁.Ki67在乳腺癌的研究進展[J].武漢大學學報:醫學版, 2011, 32(6):852-856.
18.	徐玲, 劉蔭華, 葉京明, 等.乳腺癌組織Ki67表達與恩環類聯合紫杉類新輔助化療效果的相關性[J].中華外科雜志, 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.	俸瑞發, 柏璐, 鄭默然, 等.乳腺癌組織HIF-1α、Ki67及VEGF表達的臨床意義[J].中華內分泌外科雜志, 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.	樸正日, 金全金, 申龍河.Ki67在乳腺癌組織中表達及其與C-erbB-2、ER、PR、P53基因的關系[J].中國民康醫學, 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, 吳驥, 顧書成, 等.survivin與p53、Ki67在復發轉移性乳腺癌組織中表達及相關性研究[J].中國普外基礎與臨床雜志, 2011, 18(3):290-294.
26.	段倞彥.ki67蛋白在乳腺癌組織中的表達及臨床意義[J].中國醫藥指南, 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.	賈靜, 孟令華.乳腺癌組織中BCSG1和Ki67的表達與臨床意義[J].河北醫藥, 2012, 34(9):1295-1297.
29.	郭彥偉.ki67在乳腺癌組織中的表達及其臨床意義[J].中國臨床實用醫學, 2009, 3(4):97-98.
30.	劉廣舒, 高云, 郭鵬, 等.C-erbB-2、Ki67、nm23基因表達與乳腺癌腋窩淋巴結轉移的相關性分析[J].實用預防醫學, 2013, 20(3):340-342.
31.	王建法, 顧超, 葉宣光.乳腺癌淋巴結轉移與Ki67、VEGF表達的相關性及其臨床意義[J].實用癌癥雜志, 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, 陳卓榮, 黃湛, 等.Ki67在不同分子類型乳腺癌組織中的表達及意義[J].實用癌癥雜志, 2012, 27(3):247-249.
34.	徐婷, 何奇, 吳克瑾, 等.三陰性乳腺癌中p53和Ki67表達的相關研究[J].上海交通大學學報:醫學版, 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.	L?nning PE.Poor-prognosis estrogen receptor-positive disease:present and future clinical solutions[J].Ther Adv Med Oncol, 2012, 4(3):127-137.
37.	張同先, 王亞紅, 張巍, 等.Ki67作為ER+和(或) PR+乳腺癌進一步分型指標的研究[J].實用醫學雜志, 2013, 29(3):374-377.
38.	張好云, 陳天文, 王開昕, 等.Ki67表達在乳腺癌新輔助化療中的臨床意義[J].實用醫院臨床雜志, 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, 雷玉濤, 等.乳腺癌新輔助化療療效及ER/PR, HER2, Ki67, CyclinA2的化療預測作用[J].中國微創外科雜志, 2011, 11(2):163-167.
41.	韋祝新, 王紹豐.惡性腫瘤生物特性與Ki67基因表達的關系研究進展[J].中國醫藥導刊, 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. 楊樺, 王思愚, 區偉, 等.華南地區年輕乳腺癌患者的臨床特征及預后因素分析[J].癌癥, 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. 馬志君, 吉潔.Ki67與腫瘤關系的研究進展[J].中國醫療前沿, 2012, 7(7):15-17.
5. 鄧秀娟, 吳海根.PTEN、Ki67在卵巢惡性腫瘤組織中的研究進展[J].現代腫瘤醫學, 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. 韓益玲, 陳芳源, 鐘璐.Ki67抗原在白血病研究中的應用[J].診斷學理論與實踐, 2008, 7(3):348-351.
14. 程廣保, 吳璟霞.乳腺癌發病的基因調控機制[J].現代腫瘤醫學, 2010, 18(9):1848-1852.
15. 王合兵, 肖堅, 陳文新.ER、PR、p53及HER-2在113例乳腺癌中的表達及臨床意義[J].腫瘤學雜志, 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. 楊雪琴, 李雁.Ki67在乳腺癌的研究進展[J].武漢大學學報:醫學版, 2011, 32(6):852-856.
18. 徐玲, 劉蔭華, 葉京明, 等.乳腺癌組織Ki67表達與恩環類聯合紫杉類新輔助化療效果的相關性[J].中華外科雜志, 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. 俸瑞發, 柏璐, 鄭默然, 等.乳腺癌組織HIF-1α、Ki67及VEGF表達的臨床意義[J].中華內分泌外科雜志, 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. 樸正日, 金全金, 申龍河.Ki67在乳腺癌組織中表達及其與C-erbB-2、ER、PR、P53基因的關系[J].中國民康醫學, 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, 吳驥, 顧書成, 等.survivin與p53、Ki67在復發轉移性乳腺癌組織中表達及相關性研究[J].中國普外基礎與臨床雜志, 2011, 18(3):290-294.
26. 段倞彥.ki67蛋白在乳腺癌組織中的表達及臨床意義[J].中國醫藥指南, 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. 賈靜, 孟令華.乳腺癌組織中BCSG1和Ki67的表達與臨床意義[J].河北醫藥, 2012, 34(9):1295-1297.
29. 郭彥偉.ki67在乳腺癌組織中的表達及其臨床意義[J].中國臨床實用醫學, 2009, 3(4):97-98.
30. 劉廣舒, 高云, 郭鵬, 等.C-erbB-2、Ki67、nm23基因表達與乳腺癌腋窩淋巴結轉移的相關性分析[J].實用預防醫學, 2013, 20(3):340-342.
31. 王建法, 顧超, 葉宣光.乳腺癌淋巴結轉移與Ki67、VEGF表達的相關性及其臨床意義[J].實用癌癥雜志, 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, 陳卓榮, 黃湛, 等.Ki67在不同分子類型乳腺癌組織中的表達及意義[J].實用癌癥雜志, 2012, 27(3):247-249.
34. 徐婷, 何奇, 吳克瑾, 等.三陰性乳腺癌中p53和Ki67表達的相關研究[J].上海交通大學學報:醫學版, 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. L?nning PE.Poor-prognosis estrogen receptor-positive disease:present and future clinical solutions[J].Ther Adv Med Oncol, 2012, 4(3):127-137.
37. 張同先, 王亞紅, 張巍, 等.Ki67作為ER+和(或) PR+乳腺癌進一步分型指標的研究[J].實用醫學雜志, 2013, 29(3):374-377.
38. 張好云, 陳天文, 王開昕, 等.Ki67表達在乳腺癌新輔助化療中的臨床意義[J].實用醫院臨床雜志, 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, 雷玉濤, 等.乳腺癌新輔助化療療效及ER/PR, HER2, Ki67, CyclinA2的化療預測作用[J].中國微創外科雜志, 2011, 11(2):163-167.
41. 韋祝新, 王紹豐.惡性腫瘤生物特性與Ki67基因表達的關系研究進展[J].中國醫藥導刊, 2011, 13(8):1388-1389.

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Correlative Research of Ki-67 Antigen in Breast Cancer

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