Correlation between Ki67 and Breast Cancer Prognosis

Oncology (Switzerland)

Volumn 84, Issue 4, 2013, Pages 219-225

  Kontzoglou, Konstantinos ^a   Palla, Victoria ^c   Karaolanis, George ^d   Karaiskos, Ioannis ^a   Alexiou, Ioannis ^a   Pateras, Ioannis ^a   Konstantoudakis, Konstantinos ^e   Stamatakos, Michael ^b  

^a UNIVERSITY OF ATHENS   (Greece)

^b N Athinaion   (Greece)

^c Andreas Papandreou General Hospital   (Greece)

^d Medic Medical Center   (Greece)

^e Bostanio General Hospital   (Greece)

Author keywords

Breast cancer; Ki67; Prognosis; Tumor proliferation marker

Indexed keywords

ANTINEOPLASTIC AGENT; ESTROGEN RECEPTOR; KI 67 ANTIGEN; PROGESTERONE RECEPTOR;

ANTIGEN DETECTION; ANTIGEN EXPRESSION; ANTIGEN FUNCTION; BREAST CANCER; CANCER ADJUVANT THERAPY; CANCER PROGNOSIS; HUMAN; MEDLINE; NONHUMAN; PRIORITY JOURNAL; REVIEW; BREAST; BREAST CARCINOMA; DECISION MAKING; DISEASE FREE SURVIVAL; IMMUNOREACTIVITY; INTRADUCTAL CARCINOMA; MEDICAL SUBJECT HEADINGS; OVERALL SURVIVAL; PUBLICATION;

BREAST NEOPLASMS; DISEASE-FREE SURVIVAL; FEMALE; HUMANS; KI-67 ANTIGEN; PREDICTIVE VALUE OF TESTS; PROGNOSIS; TUMOR MARKERS, BIOLOGICAL;

EID: 84873052471     PISSN: 00302414     EISSN: 14230232     Source Type: Journal    
DOI: 10.1159/000346475     Document Type: Review

References (77)

1. US Cancer Statistics Working Group: United States Cancer Statistics: 1999-2007 Incidence and Mortality Web-Based Report. Atlanta, Department of Health and Human Services, Centers for Disease Control and Prevention, and National Cancer Institute, 2010. http://www.cdc.gov/uscs.
2. Esteva FJ, Hortobagyi GN: Prognostic molecular markers in early breast cancer. Breast Cancer Res 2004; 6:109-118. (Pubitemid 38607664)
3. Gerdes J, Schwab U, Lemke H, Stein H: Production of a mouse monoclonal antibody reactive with a human nuclear antigen associated with cell proliferation. Int J Cancer 1983; 31:13-20. (Pubitemid 13179545)
4. Fonatsch C, Duchrow M, Rieder H, Schluter C, Gerdes J: Assignment of the human Ki67 gene (MK167) to 10q25-qter. Genomics 1991; 11:476-477.
5. Schlüter C, Duchrow M, Wohlenberg C, Becker MH, Key G, Flad HD, Gerdes J: The cell proliferation-associated antigen of antibody Ki67:a very large, ubiquitous nuclear protein with numerous repeated elements, representing a new kind of cell-cycle-maintaining proteins. J Cell Biol 1993; 123:513-522. (Pubitemid 23324910)
6. Duchrow M, Schluter C, Wohlenberg C, Flad HD, Gerdes J: Molecular characterization of the gene locus of the human cell proliferation-associated nuclear protein defined by monoclonal antibody Ki67. Cell Prolif 1996; 29:1-12. (Pubitemid 26086057)
7. Isola J, Helin H, Kallioniemi OP: Immuno-electron-microscopic localization of a proliferation-associated antigen Ki67 in MCF-7 cells. Histochem J 1990; 22:498-506. (Pubitemid 20327237)
8. Verheijen R, Kuijpers HJ, Schlingemann RO, Boehmer AL, van Driel R, Brakenhoff GJ, Ra-maekers FC: Ki67 detects a nuclear matrix-associated proliferation-related antigen. I. In-tracellular localization during interphase. J Cell Sci 1989; 92:123-130.
9. Heidebrecht HJ, Buck F, Haas K, Wacker HH, Parwaresch R: Monoclonal antibodies Ki-S3 and Ki-S5 yield new data on the 'Ki-67 proteins'. Cell Prolif 1996; 29:413-425. (Pubitemid 26345569)
10. Starborg M, Gell K, Brundell E, Höög C: The murine Ki-67 cell proliferation antigen accumulates in the nucleolar and heterochromatic regions of interphase cells and at the periphery of the mitotic chromosomes in a process essential for cell cycle progression. J Cell Sci 1996; 109:143-153.
11. Beresford MJ, Wilson GD, Makris A: Measuring proliferation in breast cancer: practicalities and applications. Breast Cancer Res 2006; 8:216.
12. Key G, Becker MH, Baron B, Duchrow M, Schlüter C, Flad HD, Gerdes J: Modalities of synthesis of Ki67 antigen during the stimulation of lymphocytes. Cytometry 1991; 12:42-49.
13. Key G, Becker MH, Baron B, Duchrow M, Schlüter C, Flad HD, Gerdes J: New Ki-67-equivalent murine monoclonal antibodies (MIB 1-3) generated against bacterially expressed parts of the Ki-67 cDNA containing three 62 base pair repetitive elements encoding for the Ki-67 epitope. Lab Invest 1993; 68: 629-636. (Pubitemid 23202791)
14. McCormick D, Yu C, Hobbs C, Hall PA: The relevance of antibody concentration to the immunohistological quantification of cell proliferation-associated antigens. Histopa-thology 1993; 22:543-547. (Pubitemid 23197955)
15. Viale G, Giobbie-Hurder A, Regan MM, Coates AS, Mastropasqua MG, Dell'Orto P, Maiorano E, MacGrogan G, Braye SG, Ohlschlegel C, Neven P, Orosz Z, Olszewski WP, Knox F, Thürlimann B, Price KN, Casti-glione-Gertsch M, Gelber RD, Gusterson BA, Goldhirsch A; Breast International Group Trial 1-98:Prognostic and predictive value of centrally reviewed Ki67 labeling index in postmenopausal women with endocrine-responsive breast cancer: results from Breast International Group Trial 1-98 comparing adjuvant tamoxifen with letrozole. J Clin Oncol 2008; 26:5569-5575.
16. Zabaglo L, Ormerod MG, Dowsett M: Measurement of proliferation marker Ki67 in breast tumour FNAs using laser scanning cy-tometry in comparison to conventional im-munocytochemistry. Cytometry B Clin Cy-tom 2003; 56:55-61. (Pubitemid 38292616)
17. Ruiz C, Seibt S, Al Kuraya K, Siraj AK, Mir-lacher M, Schraml P, Maurer R, Spichtin H, Torhorst J, Popovska S, Simon R, Sauter G: Tissue microarrays for comparing molecular features with proliferation activity in breast cancer. Int J Cancer 2006; 118:2190-2194.
18. Sapino A, Marchiò C, Senetta R, Castellano I, Macrì L, Cassoni P, Ghisolfi G, Cerrato M, D'Ambrosio E, Bussolati G: Routine assessment of prognostic factors in breast cancer using a multicore tissue microarray procedure. Virchows Arch 2006; 449:288-296. (Pubitemid 44367968)
19. Calascibetta A, Cabibi D, Rausa L, Aragona F, Barresi E, Martorana A, Sanguedolce R: Difference in Ki67 and thymidylate synthase expression in primary tumour compared with metastatic nodes in breast cancer patients. Nucleosides Nucleotides Nucleic Acids 2006; 25:1193-1196. (Pubitemid 44651872)
20. Harper-Wynne C, Ross G, Sacks N, Salter J, Nasiri N, Iqbal J, A'Hern R, Dowsett M: Effects of the aromatase inhibitor letrozole on normal breast epithelial cell proliferation and metabolic indices in postmenopausal women: a pilot study for breast cancer prevention. Cancer Epidemiol Biomarkers Prev 2002; 11: 614-621. (Pubitemid 34760819)
21. de Lima GR, Facina G, Shida JY, Chein MB, Tanaka P, Dardes RC, Jordan VC, Gebrim LH: Effects of low dose tamoxifen on normal breast tissue from premenopausal women. Eur J Cancer 2003; 39:891-898. (Pubitemid 36428620)
22. Clarke RB, Howell A, Potten CS, Anderson E: Dissociation between steroid receptor expression and cell proliferation in the human breast. Cancer Res 2007; 57:4987-4991.
23. Clarke RB: Steroid receptors and proliferation in the human breast. Steroids 2003; 68:789-794. (Pubitemid 37532401)
24. Allred DC, Mohsin SK, Fuqua SA: Histologi-cal and biological evolution of human prema-lignant breast disease. Endocr Relat Cancer 2001; 8:47-61. (Pubitemid 32520253)
25. Rudas M, Neumayer R, Gnant MF, Mittelbock M, Jakesz R, Reiner A: p53 protein expression, cell proliferation, and steroid hormone receptors in ductal and lobular in situ carcinomas of breast. Eur J Cancer 1997; 33: 39-44. (Pubitemid 27099565)
26. Shoker BS, Jarvis C, Davies MP, Iqbal M, Sib-son DR, Sloane JP: Immunodetectable cyclin D1 is associated with oestrogen receptor but not Ki67 in normal, cancerous and precancer-ous breast lesions. Br J Cancer 2001; 84:1064-1069. (Pubitemid 32448503)
27. Tavassoli FA, Devilee P (eds): World Health Organization Classification of Tumors, Tumors of the Breast and Female Genital Organs, ed 2. Lyon, IARC Press, 2003.
28. Shi P, Wang M, Zhang Q, Sun J: Lipid-rich carcinoma of the breast. A clinicopathological study of 49 cases. Tumori 2008; 94:342-346.
29. Stumpp J, Dietl J, Geppert M: Growth fraction in breast carcinoma determined by Ki-67 im-munostaining: correlation with pathological and clinical variables. Gynaecol Obstet Invest 1992; 33:47-50.
30. Pietilainen T, Lipponen P, Aaltomaa S, Eske-linen M, Kosma VM, Syrjanen K: The important prognostic value of Ki-67 expression as determined by image analysis in breast cancer. J Cancer Res Clin Oncol 1996; 122:687-692. (Pubitemid 26349023)
31. Pinder SE, Wencyk P, Sibbering DM, Bell JA, Elston CW, Nicholson R, Robertson JF, Blamey RW, Ellis IO: Assessment of the new proliferation marker MIB1 in breast carcinoma using image analysis: associations with other prognostic factors and survival. Br J Cancer 1995; 71:146-149.
32. Rudas M, Gnant MF, Mittlböck M, Neumayer R, Kummer A, Jakesz R, Reiner G, Reiner A: Thymidine labeling index and Ki-67 growth fraction in breast cancer: comparison and correlation with prognosis. Breast Cancer Res Treat 1994; 32:165-175. (Pubitemid 24313341)
33. Sasaki K, Matsumura K, Murakami T, Tsuji T: Measurement of bromodeoxyuridine labeling index, Ki-67 score and Ag-NOR count in breast carcinomas. Comparison with DNA ploidy. Oncology 1992; 49:147-153.
34. Trihia H, Murray S, Price K, Gelber RD, Go-louh R, Goldhirsch A, Coates AS, Collins J, Castiglione-Gertsch M, Gusterson BA; International Breast Cancer Study Group: Ki-67 expression in breast carcinoma: its association with grading systems, clinical parameters, and other prognostic factors-a surrogate marker? Cancer 2003; 97:1321-1331. (Pubitemid 36237320)
35. Wintzer HO, Zipfel I, Schulte-Monting J, Hellerich U, von Kleist S: Ki-67 immuno-staining in human breast tumors and its relationship to prognosis. Cancer 1991; 67:421-428.
36. Molino A, Micciolo R, Turazza M, Bonetti F, Piubello Q, Bonetti A, Nortilli R, Pelosi G, Cetto GL: Ki-67 immunostaining in 322 primary breast cancers: associations with clinical and pathological variables and prognosis. Int J Cancer 1997; 74:433-437. (Pubitemid 27400164)
37. Bader AA, Tio J, Petru E, Bühner M, Pfahlberg A, Volkholz H, Tulusan AH: T1 breast cancer: identification of patients at low risk of axillary lymph node metastases. Breast Cancer Res Treat 2002; 76:11-17. (Pubitemid 35178624)
38. Weikel W, Beck T, Mitze M, Knapstein PG: Immunohistochemical evaluation of growth fractions in human breast cancers using monoclonal antibody Ki-67. Breast Cancer Res Treat 1991; 18:149-154.
39. Wrba F, Chott A, Reiner A, Markis-Ritzinger EM, Holtzner JH: Ki-67 immunoreactivity in breast carcinomas in relation to transferrin receptor expression, estrogen receptor status and morphological criteria. An immunohis-tochemical study. Oncology 1989; 46:255-259. (Pubitemid 19160880)
40. Moriki T, Takahashi T, Kataoka H, Hiroi M, Yamane T, Hara H: Proliferation marker MIB-1 correlates well with proliferative activity evaluated by BrdU in breast cancer: an im-munohistochemical study including correlation with PCNA, p53, c-erbB-2 and estrogen receptor status. Pathol Int 1996; 46:953-961.
41. Haerslev T, Jacobsen GK, Zedeler K: Correlation of growth fraction by Ki-67 and proliferating cell nuclear antigen (PCNA) immuno-histochemistry with histopathological parameters and prognosis in primary breast carcinomas. Breast Cancer Res Treat 1996; 37: 101-113. (Pubitemid 26030089)
42. Liu S, Edgerton SM, Moore DH, Thor AD: Measures of cell turnover (proliferation and apoptosis) and their association with survival in breast cancer. Clin Cancer Res 2001; 7: 1716-1723. (Pubitemid 32708640)
43. Nicholson RI, McClelland RA, Finlay P, Eaton CL, Gullick WJ, Dixon AR, Robertson JF, Ellis IO, Blamey RW: Relationship between EGF-R, c-erbB-2 protein expression and Ki67 immunostaining in breast cancer and hormone sensitivity. Eur J Cancer 1993; 29:1018-1023. (Pubitemid 23126705)
44. Gasparini G, Pozza F, Meli S, Reitano M, San-tini G, Bevilacqua P: Breast cancer cell kinetics: immunocytochemical determination of growth fractions by monoclonal antibody Ki-67 and correlation with flow cytometric S-phase and with some features of tumor aggressiveness. Anticancer Res 1991; 11:2015-2021.
45. Ali HR, Dawson SJ, Blows FM, Provenzano E, Leung S, Nielsen T, Pharoah PD, Caldas C: A Ki67/BCL2 index based on immunohisto-chemistry is highly prognostic in ER-positive breast cancer. J Pathol 2012; 226:97-107.
46. Millar EK, Dean JL, McNeil CM, O'Toole SA, Henshall SM, Tran T, Lin J, Quong A, Com-stock CE, Witkiewicz A, Musgrove EA, Rui H, Lemarchand L, Setiawan VW, Haiman CA, Knudsen KE, Sutherland RL, Knudsen ES: Cyclin D1b protein expression in breast cancer is independent of cyclin D1a and associated with poor disease outcome. Oncogene 2009; 28:1812-1820.
47. Gandhari M, Arens N, Majety M, Dorn-Beineke A, Hildenbrand R: Urokinase-type plasminogen activator induces proliferation in breast cancer cells. Int J Oncol 2006; 28: 1463-1470.
48. Xie M, Zhu X, Liu Z, Shrubsole M, Varma V, Mayer IA, Dai Q, Chen Q, You S: Membrane progesterone receptor alpha as a potential prognostic biomarker for breast cancer survival: a retrospective study. PLoS One 2012; 7:e35198.
49. Li C, Li R, Song H, Wang D, Feng T, Yu X, Zhao Y, Liu J, Yu X, Wang Y, Geng J: Significance of AEG-1 expression in correlation with VEGF, microvessel density and clinico-pathological characteristics in triple-negative breast cancer. J Surg Oncol 2011; 103:184-192.
50. Mylona E, Nomikos A, Magkou C, Kamberou M, Papassideri I, Keramopoulos A, Nakopou-lou L: The clinicopathological and prognostic significance of membrane type 1 matrix me-talloproteinase (MT1-MMP) and MMP-9 according to their localization in invasive breast carcinoma. Histopathology 2007; 50:338-347. (Pubitemid 46169418)
51. Schröder C, Witzel I, Müller V, Krenkel S, Wirtz RM, Jänicke F, Schumacher U, Milde-Langosch K: Prognostic value of intercellular adhesion molecule (ICAM)-1 expression in breast cancer. J Cancer Res Clin Oncol 2011; 137:1193-1201.
52. Neri A, Megha T, Bettarini F, Tacchini D, Mastrogiulio MG, Marrelli D, Pinto E, Tosi P: Is tissue inhibitor of metalloproteinase-1 a new prognosticator for breast cancer? An analysis of 266 cases. Hum Pathol 2012; 43: 1184-1191.
53. Schinbeck C, Kampik T, Janni W, Rack B, Jeschke U, Krajewski S, Sommer H, Friese K: Prognostic relevance of disseminated tumor cells in the bone marrow and biological factors of 265 primary breast carcinomas. Breast Cancer Res 2005; 7:R1174-R1185.
54. Wiesner FG, Magener A, Fasching PA, Wesse J, Bani MR, Rauh C, Jud S, Schrauder M, Loehberg CR, Beckmann MW, Hartmann A, Lux MP: Ki-67 as a prognostic molecular marker in routine clinical use in breast cancer patients. Breast 2009; 18:135-141.
55. Urruticoechea A, Smith IE, Dowsett M: Proliferation marker Ki-67 in early breast cancer. J Clin Oncol 2005; 23:7212-7220.
56. de Azambuja E, Cardoso F, de Castro G Jr, Colozza M, Mano MS, Durbecq V, Sotiriou C, Larsimont D, Piccart-Gebhart MJ, Paesmans M: Ki67 as prognostic marker in early breast cancer: a meta-analysis of published studies involving 12, 155 patients. Br J Cancer 2007; 96:1504-1513. (Pubitemid 46762956)
57. Stuart-Harris R, Caldas C, Pinder SE, Pharo-ah P: Proliferation markers and survival in early breast cancer: a systematic review and meta-analysis of 85 studies in 32, 825 patients. Breast 2008; 17:323-334.
58. Jacquemier J, Charafe-Jauffret E, Monville F, Esterni B, Extra JM, Houvenaeghel G, Xerri L, Bertucci F, Birnbaum D: Association of GATA3, p53, Ki67 status and vascular peritu-moral invasion are strongly prognostic in lu-minal breast cancer. Breast Cancer Res 2009; 11:R23.
59. Molino A, Pedersini R, Micciolo R, Frisin-ghelli M, Giovannini M, Pavarana M, Nortilli R, Santo A, Manno P, Padovani M, Piubello Q, Cetto GL: Relationship between the thymi-dine labeling and Ki67 proliferative indices in 126 breast cancer patients. Appl Immunohis-tochem Mol Morphol 2002; 10:304-309. (Pubitemid 35453687)
60. Klintman M, Bendahl PO, Grabau D, Lövgren K, Malmström P, Fernö M; South Sweden Breast Cancer Group: The prognostic value of Ki67 is dependent on estrogen receptor status and histological grade in premenopausal patients with node-negative breast cancer. Mod Pathol 2010; 23:251-259.
61. Pinto AE, André S, Pereira T, Nóbrega S, Soares J: Prognostic comparative study of S-phase fraction and Ki-67 index in breast carcinoma. J Clin Pathol 2001; 54:543-549. (Pubitemid 32642944)
62. Penault-Llorca F, Abrial C, Raoelfils I, Chollet P, Cayre A, Mouret-Reynier MA, Thivat E, Mishellany F, Gimbergues P, Durando X: Changes and predictive and prognostic value of the mitotic index, Ki-67, cyclin D1, and cy-clo-oxygenase-2 in 710 operable breast cancer patients treated with neoadjuvant chemotherapy. Oncologist 2008; 13:1235-1245.
63. Railo M, Lundin J, Haglund C, von Smitten K, Nordling S: Ki-67, p53, ER receptors, ploidy and S phase as long-term prognostic factors in T1 node-negative breast cancer. Tumour Biol 2007; 28:45-51. (Pubitemid 46012465)
64. Billgren AM, TAni E, Liedberg A, Skoog L, Rutqvist LE: Prognostic significance of tumor cell proliferation analyzed in fine needle aspirates from primary breast cancer. Breast Cancer Res Treat 2002; 71:161-170. (Pubitemid 34145373)
65. Eichbaum MH, Kaltwasser M, Bruckner T, de Rossi TM, Schneeweiss A, Sohn C: Prognostic factors for patients with liver metastases from breast cancer. Breast Cancer Res Treat 2006; 96:53-62.
66. Colozza M, Sidoni A, Piccart-Gebhart M: Value of Ki67 in breast cancer: the debate is still open. Lancet Oncol 2010; 11:414-415.
67. Mengel M, von Wasielewski R, Wiese B, Rüdiger T, Müller-Hermelink HK, Kreipe H: Inter-laboratory and inter-observer reproduc-ibility of immunohistochemical assessment of the Ki-67 labelling index in a large multi-centre trial. J Pathol 2002; 198:292-299. (Pubitemid 35277379)
68. Offersen BV, Sørensen FB, Knoop A, Over-gaard J; Danish Breast Cancer Cooperative Tumour Biology Committee: The prognostic relevance of estimates of proliferative activity in early breast cancer. Histopathology 2003; 43:573-582. (Pubitemid 38002346)
69. Demichelis F, Barbareschi M, Dalla Palma P, Forti S: The virtual case: a new method to completely digitize cytological and histologi-cal slides. Virchows Arch 2002; 441:159-164. (Pubitemid 34983983)
70. Fasanella S, Leonardi E, Cantaloni C, Eccher C, Bazzanella I, Aldovini D, Bragantini E, Mo-relli L, Cuorvo LV, Ferro A, Gasperetti F, Ber-landa G, Dalla Palma P, Barbareschi M: Pro-liferative activity in human breast cancer: Ki-67 automated evaluation and the influence of different Ki-67 equivalent antibodies. Diagn Pathol 2011; 6:S7.
71. Luporsi E, André F, Spyratos F, Martin PM, Jacquemier J, Penault-Llorca F, Tubiana-Ma-thieu N, Sigal-Zafrani B, Arnould L, Gompel A, Egele C, Poulet B, Clough KB, Crouet H, Fourquet A, Lefranc JP, Mathelin C, Rouyer N, Serin D, Spielmann M, Haugh M, Chenard MP, Brain E, de Cremoux P, Bellocq JP: Ki-67: level of evidence and methodological considerations for its role in the clinical management of breast cancer: analytical and critical review. Breast Cancer Res Treat 2012; 132: 895-915.
72. Goldhirsch A, Wood WC, Coates AS, Gelber RD, Thürlimann B, Senn HJ; Panel members: 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. Ann Oncol 2011; 22:1736-1747.
73. Dowsett M, Nielsen TO, A'Hern R, Bartlett J, Coombes RC, Cuzick J, Ellis M, Henry NL, Hugh JC, Lively T, McShane L, Paik S, Penault-Llorca F, Prudkin L, Regan M, Salter J, Sotiriou C, Smith IE, Viale G, Zujewski JA, Hayes DF; International Ki-67 in Breast Cancer Working Group: Assessment of Ki67 in breast cancer: recommendations from the International Ki67 in Breast Cancer working group. J Natl Cancer Inst 2011; 103:1656-1664.
74. Ali HR, Dawson SJ, Blows FM, Provenzano E, Pharoah PD, Caldas C: Aurora kinase A outperforms Ki67 as a prognostic marker in ERpositive breast cancer. Br J Cancer 2012; 106: 1798-1806.
75. Scholzen T, Gerdes J: The Ki67 protein: from the known to the unknown. J Cell Physiol 2000; 182:311-322.
76. Neri A, Marrelli D, Pedrazzani C, Caruso S, De Stefano A, Mariani F, Megha T, De Marco G, Corso G, Pinto E, Roviello F: Prognostic relevance of proliferative activity evaluated by Mib-1 immunostaining in node negative breast cancer. Eur J Surg Oncol 2008; 34: 1299-1303.
77. Beenken SW, Bland KI: Biomarkers for breast cancer. Minerva Chir 2002; 57:437-448. (Pubitemid 34875566)