Immunohistochemical expression of Ki-67 in invasive breast carcinoma and its correlation with prognostic parameters
Keywords:
Breast carcinoma, Histological grade, Ki-67
Abstract
Background: Ki-67 expression is strictly associated with cellular proliferation and is an excellent marker for determining the growth fraction of a given cell population. It may be considered as alternative to mitotic counts in grading schemes and as a single parameter that can be used in fine needle aspirates and small biopsies. The aim of this study was to evaluate proliferative fraction of Ki67 expression in invasive breast carcinoma and to find out the correlation between Ki67 expression and clinico-pathological prognostic factors such as tumor size, lymph node status, histological grade and Nottingham prognostic index.
Materials and Methods: Seventy cases of infiltrating ductal carcinoma breast were studied. Immunohistochemistry using the anti-Ki-67 antibody [MIB-1] was performed on all cases and Ki-67 staining was categorized as low and high grade.
Result: High expression of Ki-67 was found in 71.05% cases of breast tumor with positive lymph node metastasis and 92.31% cases of Grade III tumor. Ki-67 expression was significantly associated with nodal status (p<0.0001) and poorly differentiated tumor (p<0.0001). Although, Ki-67 expression was associated with tumor size, but their correlation was not statistically significant (p= 0.065).
Conclusion: High Ki-67 expression was associated with a higher grade of malignancy. Conclusively, proliferative activity determined by Ki-67 expression may reflect the aggressive behavior of breast carcinoma. Ki-67 detection provides valuable information about proliferative activity of cells so, it is necessary to combine this with other parameters for better prognosis.
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References
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25. Nishimura R, Osako T, Okumura Y, Hayashi M, Toyozumi Y, Arima N. Ki-67 as a prognostic marker according to breast cancer subtype and a predictor of recurrence time in primary breast cancer. Experimental and therapeutic medicine. 2010 Sep 1; 1(5):747-54.
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27. Kumaki N, Umemura S, Tang X, Saito Y, Suzuki Y, Tokuda Y. Alteration of immunohistochemical biomarkers between pre-and post-chemotherapy: hormone receptors, HER2 and Ki-67. Breast Cancer. 2011 Apr 1; 18(2):98-102.
28. Dowsett M, Smith IE, Ebbs SR, Dixon JM, Skene A, A'Hern R, Salter J, Detre S, Hills M, Walsh G. Prognostic value of Ki67 expression after short-term presurgical endocrine therapy for primary breast cancer. Journal of the National Cancer Institute. 2007 Jan 17; 99(2):167-70.
2. Carter D, Schnitt SJ, Millis RR. The Breast. In: Millis SE. Sternberg’s diagnostic surgical pathology. Philadelphia: Lippincott Williams & Wilkins; 2010. p. 285-345.
3. Wirapati P, Sotiriou C, Kunkel S, et al. Meta-analysis of gene expression profiles in breast cancer: toward a unified understanding of breast cancer subtyping and prognosis signatures. Breast Cancer Res. 2008 Jan 1; 10(4):R65.
4. Stuart-Harris R, Caldas C, Pinder SE, Pharoah P. Proliferation markers and survival in early breast cancer: a systematic review and meta-analysis of 85 studies in 32,825 patients. The Breast. 2008 Aug 31; 17(4):323-34.
5. Garcia RL, Coltrera MD, Gown AM. Analysis of proliferative grade using anti-PCNA/cyclin monoclonal antibodies in fixed, embedded tissues. Comparison with flow cytometric analysis. The American journal of pathology. 1989 Apr; 134(4):733-739.
6. Schlüter C, Duchrow M, Wohlenberg C, Becker MH, Key G, Flad HD, Gerdes J. 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. The Journal of cell biology. 1993 Nov 1; 123(3):513-22.
7. Gerdes J, Schwab U, Lemke H, Stein H. Production of a mouse monoclonal antibody reactive with a human nuclear antigen associated with cell proliferation. International journal of cancer. 1983 Jan 15; 31(1):13-20.
8. Gerdes J, Lemke HI, Baisch HE, Wacker HH, Schwab U, Stein H. Cell cycle analysis of a cell proliferation-associated human nuclear antigen defined by the monoclonal antibody Ki-67. The Journal of Immunology. 1984 Oct 1; 133(4):1710-15.
9. Cooper LS, Gillett CE, Smith P, Fentiman IS, Barnes DM. Cell proliferation measured by MIB1 and timing of surgery for breast cancer. British journal of cancer. 1998 May; 77(9):1502-07.
10. Dowsett M, Nielsen TO, A’Hern R, Bartlett J, Coombes RC, Cuzick J, Ellis M, Henry NL, Hugh JC, Lively T, McShane L. Assessment of Ki67 in breast cancer: recommendations from the International Ki67 in Breast Cancer working group. Journal of the National Cancer Institute. 2011 Sep 29; 103: 1656-64.
11. Paik S, Tang G, Shak S, Kim C, Baker J, Kim W, Cronin M, Baehner FL, Watson D, Bryant J, Costantino JP. Gene expression and benefit of chemotherapy in women with node-negative, estrogen receptor–positive breast cancer. Journal of clinical oncology. 2006 Aug 10; 24(23):3726-34.
12. Paik S, Shak S, Tang G, Kim C, Baker J, Cronin M, Baehner FL, Walker MG, Watson D, Park T, Hiller W. A multigene assay to predict recurrence of tamoxifen-treated, node-negative breast cancer. New England Journal of Medicine. 2004 Dec 30; 351(27):2817-26.
13. Railo M, Nordling S, Von Boguslawsky K, Leivonen M, Kyllönen L, Von Smitten K. Prognostic value of Ki-67 immunolabelling in primary operable breast cancer. British journal of cancer. 1993 Sep; 68(3):579.
14. Yerushalmi R, Woods R, Ravdin PM, Hayes MM, Gelmon KA. Ki67 in breast cancer: prognostic and predictive potential. The lancet oncology. 2010 Feb 28; 11(2):174-83.
15. Urruticoechea A, Smith IE, Dowsett M. Proliferation marker Ki-67 in early breast cancer. Journal of clinical oncology. 2005 Oct 1; 23(28):7212-20.
16. Inwald EC, Klinkhammer-Schalke M, Hofstädter F, Zeman F, Koller M, Gerstenhauer M, Ortmann O. Ki-67 is a prognostic parameter in breast cancer patients: results of a large population-based cohort of a cancer registry. Breast cancer research and treatment. 2013 Jun 1; 139(2):539-52.
17. Davis BW, Gelber R, Goldhirsch A, Hartmann WH, Hollaway L, Russell I, Rudenstam CM, Ludwig Breast Cancer Study Group. Prognostic significance of peritumoral vessel invasion in clinical trials of adjuvant therapy for breast cancer with axillary lymph node metastasis. Human pathology. 1985 Dec 31; 16(12):1212-8.
18. Contesso G, Mouriesse H, Friedman S, Genin J, Sarrazin D, Rouesse J. The importance of histologic grade in long-term prognosis of breast cancer: a study of 1,010 patients, uniformly treated at the Institut Gustave-Roussy. Journal of Clinical Oncology. 1987 Sep 1; 5(9):1378-86.
19. Franklin WA, Bibbo M, Doria MI, Dytch HE, Toth J, DeSombre E, Wied GL. Quantitation of estrogen receptor content and Ki-67 staining in breast carcinoma by the microTICAS image analysis system. Analytical and quantitative cytology and histology. 1987 Aug; 9(4):279-86.
20. Stefano DD, Mingazzini PL, Scucchi L, Donnetti M, Marinozzi V. A comparative study of histopathology, hormone receptors, peanut lectin binding, ki‐67 immunostaining, and nucleolar organizer region‐associated proteins in human breast cancer. Cancer. 1991 Jan 15; 67(2):463-71.
21. Barbareschi M, Leonardi E, Mauri FA, Serio G, Dalla Palma P. p53 and c-erbB-2 protein expression in breast carcinomas. An immunohistochemical study including correlations with receptor status, proliferation markers, and clinical stage in human breast cancer. American journal of clinical pathology. 1992 Oct; 98(4):408-18.
22. Trihia H, Murray S, Price K, Gelber RD, Golouh R, Goldhirsch A, Coates AS, Collins J, Castiglione-Gertsch M, Gusterson BA. Ki-67 expression in breast carcinoma: its association with grading systems, clinical parameters, and other prognostic factors--a surrogate marker? Cancer. 2003 Mar; 97(5):1321-31.
23. Ermiah E, Buhmeida A, Abdalla F, Khaled BR, Salem N, Pyrhönen S, Collan Y. Prognostic value of proliferation markers: immunohistochemical ki-67 expression and cytometric s-phase fraction of women with breast cancer in Libya. J Cancer. 2012 Jan 1; 3:421-31.
24. 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 peritumoral invasion are strongly prognostic in luminal breast cancer. Breast Cancer Res. 2009 Apr 30; 11(2):R23.
25. Nishimura R, Osako T, Okumura Y, Hayashi M, Toyozumi Y, Arima N. Ki-67 as a prognostic marker according to breast cancer subtype and a predictor of recurrence time in primary breast cancer. Experimental and therapeutic medicine. 2010 Sep 1; 1(5):747-54.
26. Midulla C, De Iorio P, Nagar C, Pisani T, Cenci M, Valli C, Nofroni I, Vecchione A. Immunohistochemical expression of p53, nm23-HI, Ki67 and DNA ploidy: correlation with lymph node status and other clinical pathologic parameters in breast cancer. Anticancer research. 1998 Dec; 19(5B):4033-37.
27. Kumaki N, Umemura S, Tang X, Saito Y, Suzuki Y, Tokuda Y. Alteration of immunohistochemical biomarkers between pre-and post-chemotherapy: hormone receptors, HER2 and Ki-67. Breast Cancer. 2011 Apr 1; 18(2):98-102.
28. Dowsett M, Smith IE, Ebbs SR, Dixon JM, Skene A, A'Hern R, Salter J, Detre S, Hills M, Walsh G. Prognostic value of Ki67 expression after short-term presurgical endocrine therapy for primary breast cancer. Journal of the National Cancer Institute. 2007 Jan 17; 99(2):167-70.
CITATION
DOI: 10.17511/ijmrr.2016.i05.17
Published: 2016-05-31
How to Cite
1.
Jain R, Malik R, Trichal V, Jain A, Bakna M. Immunohistochemical expression of Ki-67 in invasive breast carcinoma and its correlation with prognostic parameters. Int J Med Res Rev [Internet]. 2016May31 [cited 2024Nov.8];4(5):765-70. Available from: https://ijmrr.medresearch.in/index.php/ijmrr/article/view/554
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