Ki-67 Protein as a Prognostic Indicator in Ovarian Carcinoma

Rima Melati Mat Satar, Zed Zakari Abdul Hamid, Hartini Yusuf, Maimunah Mustakim


Ki-67 expression is strongly correlated with tumour cell proliferation and growth. It is widely used as a proliferation marker in the routine pathological investigation. The nuclear protein Ki-67 (pKi67) is recognised prognostic and predictive indicator for the biopsies assessment for cancer patients. Clinically, pKi67 has been revealed to associate with metastasis and the clinical stage of tumours. Furthermore, it has been presented that the expression of Ki-67 is significantly higher in malignant tissues with poorly differentiated tumour cells, as compared with normal tissue. The Ki-67 labelling index plays a vital role as an independent prognostic factor for survival rate, which includes all stages and grade categories. There is an association between the ratios of Ki-67 positive malignant cells and patient survival. This review provides an overview of recent advances in detecting Ki-67 in ovarian carcinoma.


Immunostaining, Ki-67, proliferation marker, prognostic factor, patient survival

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Aune, G., Stunes, A.K, Tingulstad, S., Salvesen, O., Syversen, U., Torp, S.H. (2011). The proliferation markers Ki 67 / MIB 1, phosphohist. One H3, and survivin may contribute in the identification of aggressive ovarian carcinomas. Int J Clin Exp Pathol. ;4(5):444-53.

Bast, R.C., Hennessy, B. & Mills, G.B. (2009). The biology of ovarian cancer: new opportunities for translation. Nature Reviews Cancer 9 (6): 415-428.

Brown, D.C. and Gatter, K.C. (2002). Ki67 protein: the immaculate deception? Histopathology 40: 2 11.

Chang, J., Ormerod, M., Powles, T.J., Allred, D.C., Ashley, S. E. Dowsett, M. (2000) Apoptosis and prolif¬eration as predictors of chemotherapy response in patients with breast carcinoma. Cancer 89:2145 2152.<2145::AID-CNCR1>3.0.CO;2-S

Choudhury M, Goyal S, Pujani M. (2011) A cytohistological study of Ki-67 expression in ovarian tumours. Indian J Pathol Microbiol.;54(1):21–24.

Ciancio N, Galasso MG, Campisi R, et al., (2012) Prognostic value of p53 and Ki67 expression in fiberoptic bronchial biopsies of patients with non small cell lung cancer. Multidiscip Respir Med 7: 29.

Ezzati, M., Abdullah, A., Shariftabrizi, A., Hou, J., Kopf, M., Stedman, J. K., … Shahabi, S. (2014). Recent Advancements in Prognostic Factors of Epithelial Ovarian Carcinoma. International Scholarly Research Notices, 2014, 953509.

Ferlay, J., Soerjomataram, I., Dikshit, R., Eser, S., Mathers, C., Rebelo, M., Parkin, D.M., Forman, D. & Bray, F. (2015). Cancer incidence and mortality worldwide: Sources, methods and major patterns in GLOBOCAN 2012. International Journal of Cancer 136(5): E359-E386.

Garzetti GG, Ciavattini A, Goteri G, De Nictolis M, Stramazzotti D, Lucarini G, et al. (1995). Ki-67 antigen immunostaining (MIB-1 monoclonal antibody) in serous ovarian tumours: index of proliferative activity with prognostic signif-icance. Gynecol Oncol.56:169–74.

Giurgea LN, Ungureanu C, Mihailovici MS. (2012). The immunohistochemical expression of p53 and Ki67 in ovarian epithelial borderline tumours. Correlation with clinicopathological factors. Rom J Morphol Embryol. 53(4):967-73.

Gursan, N., Sipal, S., Calik, M., & Gundogdu, C. (2009). P53, Bcl-2, Ki-67 Li (Labeling Index) Status in Benign, Proliferative, And Malignant Ovarian Surface Epithelial Neoplasms. The Eurasian Journal of Medicine, 41(1), 10–14.


Hartozinska A, Bar JK, Sedlaczek P, Gerber J. (1995). Expression of p53 protein and Ki-67 reactivity in ovarian neoplasms. Anatomic Pathology, 105:334-340.

Heeran MC, Høgdall CK, Kjaer SK, Christensen L, Jensen A, Blaakaer J, et al. (2013). Prognostic value of tissue protein expression levels of MIB-1 (Ki-67) in Danish ovarian cancer patients. From the 'MALOVA' ovarian cancer study. APMIS, 121(12):1177-86.

Hooghe, B., Hulpiau, P., van Roy, F., & De Bleser, P. (2008). ConTra: a promoter alignment analysis tool for identification of transcription factor binding sites across species. Nucleic Acids Research, 36(Web Server issue), W128–W132.

Iatropoulos, M. J. and Williams, G. M. (1996). Proliferation markers. Exp Toxicol Pathol 48: 175 181.

Ishihara, M., Mukai, H., Nagai, S., et al., (2013). Retrospective analysis of risk factors for central nervous system metastases in operable breast cancer: effects of biologic subtype and Ki67 overex¬pression on survival. Oncology 84: 135 140.

Itamochi, H., Kigawa, J., Sugiyama, T., Kikuchi, Y., Suzuki, M., Terakawa, N. (2002). Low proliferation activity may be associated with chemoresistance in clear cell carcinoma of the ovary. Obset Gynecol. 100:281-87.

Jacquemier, J.D., Penault Llorca, F.M., Bertucci, F, et al. (1998). Angiogenesis as a prognostic marker in breast carcinoma with conventional adjuvant chemotherapy: a multiparametric and immunohistochemical analysis. J Pathol 184: 130 135, 1998.<130::AID-PATH19>3.0.CO;2-W

Josefsson, A., Wikström, P., Egevad, L., et al. (2012). Low endoglin vascular density and Ki67 index in Gleason score 6 tumours may identify prostate cancer patients suitable for surveillance. Scand J Urol Nephrol 46: 247 257.

Kaern J, Aghmesheh M, Nesland JM, Danielsen HE, Sandstad B, Friedlander M, Tropé C. (2005). Prognostic factors in ovarian carcinoma stage III patients. Can biomarkers improve the prediction of short- and long-term survivors? International Journal of Gynecological Cancer 15(6):1014–22.

Kausch, I., Lingnau, A., Endl, E., Sellman, K., Deinert, I., Ratliff, T.L., Böhle, A. (2003) Antisense treatment against Ki 67 mRNA inhibits proliferation and tumor growth in vitro and in vivo. Int J Cancer 105: 710 716, 2003.

Khandakar, B., Sandeep, R.. Mathur, R., Kumar, L., Kumar S, Gupta S. D., Iyer, V.K., M. Kalaivani (2014). Tissue Biomarkers in Prognostication of Serous Ovarian Cancer following Neoadjuvant Chemotherapy. BioMed Research International. 401245, 9 pages,

Khouja. M.H., Baekelandt, M., Nesland, J.M., Holm, R. (2007). The Clinical Importance of Ki- 67, p16, p14, and p57 Expression in patients with advanced ovarian carcinoma. Int J Gynecol Pathol. 26:418-25. doi: 10.1097/pgp.0b013e31804216a0

Klöppel, G., Perren, A., Heitz, P.U. (2004). The gastroenteropancreatic neuroendocrine cell system and its tumors: the WHO classifi¬cation. Ann N Y Acad Sci 1014: 13 27, 2004.

Kritpracha, K., Hanprasertpong, J., Chandeying, V., Dechsukhum, C., Geater, A. (2005). Survival analysis in advanced epithelial ovarian carcinoma in relation to proliferative index of MIB -1 immunostaining. J Obstet Gynaecol Res. 31(3):268-76.

Kurman, R. J., & Shih, I.-M. (2010). The Origin and Pathogenesis of Epithelial Ovarian Cancer- a Proposed Unifying Theory. The American Journal of Surgical Pathology, 34(3), 433–443.

Lengyel, E. 2010. Ovarian cancer development and metastasis. The American Journal of Pathology 177(3): 1053-1064.

Liu. J., Fang, L., Cheng, Q., Li, L., Su, C., Zhang, B., Zheng, J (2012). Effects of G250 promoter controlled conditionally replicative adenovirus expressing Ki67 siRNA on renal cancer cell. Cancer Sci 103: 1880 1888, 2012.

Liu P, Sun YL, Du J, Hou XS, Meng H. CD (2012). 105/KI67 coexpression correlates with tumour progression and poor prognosis in epithelial ovarian cancer. Int J Gynecol Cancer. 22:586-92. doi: 10.1097/IGC.0b013e31823c36b8

Mahadevappa, A., Krishna, S. M., & Vimala, M. G. (2017). Diagnostic and Prognostic Significance of Ki-67 Immunohistochemical Expression in Surface Epithelial Ovarian Carcinoma. Journal of Clinical and Diagnostic Research : JCDR, 11(2), EC08–EC12.

Marinas, M.C, Mogos, G., Ciurea, R., Mogos, D.G. (2012). EGFR, HER2/neu and Ki67 immunoexpression in serous ovarian tumours. Romanian Journal of Morphology and Embryology. 53(3):563-67. ISSN (on-line) 2066–8279

Min, K.W., & Park, M.H. (2007). The expression of c-erbB-2, EGFR, p53 and Ki-67 in ovarian borderline tumours and carcinomas of the ovary. Korean J Pathol. 41:296- 306.

Mita, S., Nakai, A., Maeda, S. & Takeshita, T. (2004). Prognostic significance of Ki67 antigen immunostaining (MIB 1 monoclonal antibody) in ovarain cancer. J Nippon Med Sch. 71:384-91.

Modlin, I.M., Moss, S.F., Chung, D.C., Jensen, R.T., Snyderwine, E. (2008). Priorities for improving the management of gastroenteropancreatic neuroendocrine tumors. J Natl Cancer Inst 100: 1282 1289, 2008.

Munstedt, K., von Georgi, R., Franke, F.E. (2004). Correlation between MIB1 determined tumour growth fraction and incidence of tumour recurrence in early ovarian carcinomas. Cancer Invest. 22:185–9.

Ng, J.S., Low, J.J. & Ilancheran, A. 2012. Epithelial ovarian cancer. Best Practice & Research Clinical Obstetrics & Gynaecology 26(3): 337-345.

Petit, T., Wilt, M., Velten, M., Millond, R.,.Rodiere, J.-F., Borel, C., Mors, R., Haegelé, P., Eber, M., Ghnassia, J.-P. (2004). Comparative value of tumour grade, hormonal receptors, Ki 67, HER 2 and topoisomerase II alpha status as predictive markers in breast cancer patients treated with neoadjuvant anthracycline based chemotherapy. Eur J Cancer 40:205 211,.

Röhlke, P., Milde-Langosch, K., Weyland, C., Pichlmeier, U., Jonat, W., Löning, T. (1997). p53 is a persistent and predictive marker in advanced ovarian carcinomas: multivariate analysis including comparison with Ki67 immunoreactivity. J Cancer Res Clin Oncol. 123(9):496–501.

Scholzen, T., & Gerdes, J.(2000). The Ki 67 protein: from the known and the unknown. J Cell Physiol 182: 311 322.<311::AID-JCP1>3.0.CO;2-9

Shirendeb, U., Hishikawa, Y., Moriyama, S., et al. (2009).Human papil¬lomavirus infection and its possible correlation with p63 expression in cervical cancer in Japan, Mongolia, and Myanmar. Acta Histochem Cytochem 42: 181 190,

Sorbye SW, Kilvaer TK, Valkov A, et al. (2012). Prognostic impact of CD57, CD68, M CSF, CSF 1R, Ki67 and TGF beta in soft tissue sarcomas. BMC Clin Pathol 12: 7.

Sorbye, S.W., Kilvaer, T.K., Valkov, A., et al. (2012). Prognostic impact of Jab1, p16, p21, p62, Ki67 and Skp2 in soft tissue sarcomas. PLoS One 7: e47068.

Sylvia, M.T., Kumar, S., Dasari, P. (2012). The expression of immunohistochemical markers estrogen receptor, progesterone receptor, Her-2-neu, p53 and Ki-67 in epithelial ovarian tumours and its correlation with clinicopathologic variables. Indian J Pathol Microbiol. 55:33-37.

Viale, G., Maisonneuve, P., Bonoldi, E., Bacco, Di., Bevilacqua, P., Panizzoni, G.A. (1997). The combined evaluation of p53 accumulation and of Ki-67 (MIB1) labelling index provides independent information on overall survival of ovarian carcinoma patients. Annals of Oncology. 8:469-476.

Viale, G., Giobbie-Hurder, A., Regan, M. M., Coates, A. S., Mastropasqua, M. G., Dell’Orto, P., Goldhirsch, A. (2008). Prognostic and Predictive Value of Centrally Reviewed Ki-67 Labeling Index in Postmenopausal Women With Endocrine-Responsive Breast Cancer: Results From Breast International Group Trial 1-98 Comparing Adjuvant Tamoxifen With Letrozole. Journal of Clinical Oncology, 26(34), 5569–5575.

Yerushalmi R, Woods R, Ravdin, P.M., Hayes, M.H., Gelmon, K.A. (2010). Ki67 in breast cancer: prognostic and predictive potential. Lancet Oncol 11: 174 18.

Zainal, A. & Nor Saleha, I. 2011. National Cancer Registry Report: Malaysia Cancer Statistics – Data and Figure 2007. National Cancer Registry Ministry of Health Malaysia.


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