Expression of Ki-67 and Prognosis of Breast Invasive Carcinoma in Congolese Women
International Journal of Clinical Oncology and Cancer Research
Volume 3, Issue 1, February 2018, Pages: 1-9
Received: Jan. 26, 2018;
Accepted: Feb. 24, 2018;
Published: Mar. 19, 2018
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Nday Guy, Surgery Department, University of Lubumbashi, Lubumbashi, the Democratic Republic of Congo
Kabamba Michel, Department of Public Health, University of Kamina, Kamina, the Democratic Republic of Congo
Mukalay Abdon, Clinical Epidemiology Unit and Tropical Pathologies, University of Lubumbashi, Lubumbashi, the Democratic Republic of Congo
Tshilombo François, Surgery Department, University of Lubumbashi, Lubumbashi, the Democratic Republic of Congo
Odimba Etienne, Surgery Department, University of Lubumbashi, Lubumbashi, the Democratic Republic of Congo
Lebwaz Bienvenu, Pathology Department, University of Kinshasa, Kinshasa, the Democratic Republic of Congo
Kalenga Prospère, Department of Obstetrics and Gynecology, University of Lubumbashi, Lubumbashi, the Democratic Republic of Congo
Ilunga Julien, Pathology Department, University of Lubumbashi, Lubumbashi, the Democratic Republic of Congo
Breast invasive carcinoma is the most cancer in the world. In low resource countries, cancer are of poor prognosis for they are diagnosed at later stage. There is not a cancer registry in the Democratic Republic of Congo and studies on biomarkers are lacking. This study had the main purpose to determine the expression of Ki-67 and the prognosis of invasive breast carcinoma in Congolese women. Cross-sectional study of 86 women with invasive Breast Carcinoma were included in the Democratic Republic of Congo from Kinshasa (n=73) and Lubumbashi Cities (n= 13). Age at the time of diagnosis, tumor size, tumor necrosis, grade of tumor and proliferation index measured by Ki-67 were taken into account. Statistical analysis used SPSS program and Pearson Chi-square test. From 2014 to 2016, biopsies were collected from 86 Congolese patients to determine the expression of Ki-67 and the prognosis of invasive breast carcinoma. The proliferation marker was observed in 91.9%. K-i67 > 20% and > 30% were found respectively in 55.8% and in 33.7% of patients. The value of the Ki-67 was influenced by the tumor stage. The association between the size of the tumor and Ki-67 was statistically significant. The risk of tumor necrosis was 2.9 times in case of tumor with positive Ki-67. Ki-67 was positive in many patients younger than 45 years. However, the difference was not statistically significant. In patients with T3 and T4 tumors, the risk of positive Ki-67 was 7 times compared to those of T1 and T2 tumors. Patients with G3 tumors had 9 times the risk to have positive Ki-67 compared to those with G1 and G2 tumors. In conclusion, tumors in Congolese women are associated with higher proliferation index and poor prognosis for most of them are diagnosed at later stage. Chemotherapy can be justified for prior care in low resource countries and radical mastectomy should be encouraged.
Expression of Ki-67 and Prognosis of Breast Invasive Carcinoma in Congolese Women, International Journal of Clinical Oncology and Cancer Research.
Vol. 3, No. 1,
2018, pp. 1-9.
Abadie J., “techniques de détection et de quantification de la prolifération en histopathologie animale,» Fr. Histotechnol., 2003; 16, no 1, pp45-60.
Agboola A. O. J., Banjo A. A. F., Anunoni C. C., Salami B., Agboola M. D., Musa A. A., Nolan C. C., Rakha E. A., Ellis I. O., and Green A. R., «Cell Proliferation (KI-67) Expression Is Associated with Poorer Prognosis in Nigerian Compared to British Breast Cancer Women,» Oncology 2013; 8 pages.
Aktas B., Bankfalvi A., and Kasimir-Bauer S. “Evaluation and correlation of risk recurrence in early breast camcert assessed by Oncotype DX, clinicopathological makers and tumor cell dissemination in the blood and bone marrow,» Mol Clin Oncol. 2013 Nov; 1 (6):1049-1054.
Aleskandarany M. A, Green A. R, Rakha et al. “Growth fraction as a predictor of response to chemotherapy in node-negative breast cancer,” International Journal of Cancer, 2010; vol. 126, no. 7, pp. 1761-1769.
Aleskandarany M. A, Rakha E. A, Macmillan R. D, Powe D. G, Ellis I. O et al.;MIB1/ki-67 labelling index can classify grade 2 breast cancer into two clinically distinct subgroups. Breast Cancer Research and Treatment, Springer Verlag, 2011; 127 (3), pp. 591-599.
Amadori D, Serra P, Bravaccini S, Farolfi A, Puecetti M, Carretta E, Medri L, Nanni O., Tumedei MM, Kahima J, Masalu N., Differences in biological features of breast cancer between caucasian ( Italian) and African ( Tanzanian) populations, Breast cancer Res treat. 2014 May; 145 (1). 177-83.
Anders C., Johnson R., Litton J., Phillips M., and Bleyer A.. “Breast Cancer Before Age 40 years” Semin Oncol. 2009 June; 36 (3):237-249.
Annin DR, Rimm DL. Quantitative assessments Ki-67 score for prediction of response to neoadjuvant chemotherapy in breast cancer. Lab. Invest. 2014; 94 (1), 98–106.
Awadelkarfim K. D., Mariani- Costantini R., Osman I., and Barberis M. C., «Ki-67 Labeling Index in Primary Invasive Breast Cancer from Sudanese Patients: A Pilot Study,” ISRN Pathology 2012; 6 pages.
Bai Y, Tolles J, Cheng H, et al. Quantitative assessment shows loss of antigenic epitopes as a function of time to formalin fixation. Modern Pathol. 2011; 91 (8):1253–1261.
Bailes AA, Kuerer HM, Lari SA, Jones LA, Brewster A M. Impact of race and ethnicity on features and autcome of ductal carcinoma in situ of the breast. Cancer. 2013 Jan1; 119 (1):150-7Brown JR, Digiovanna MP, Killelea B, L.
Camp RL, Charette LA, Rimm DL. Validation of tissue microarray technology in breast carcinoma. Lab Invest. 2000; 80 (12):1943–1949.
Carey LA, Perou CM, Livasy CA et al. Race, breast cancer subtypes, and survival in the Carolina Breast Cancer Study. JAMA 2006; 295:2492–2502.
Cattoretti G, Becker MH, Key G, et al. Monoclonal antibodies against recombinant parts of the Ki-67 antigen (MIB 1 and MIB 3) detect proliferating cells in microwave-processed formalin-fixed paraffin sections. J Pathol. 1992; 168 (4):357–363.
Cheang MC, Voduc D, Bajdik C, et al. Basal-like breast cancer defined by five biomarkers has superior prognostic value than triple-negative phenotype. Clin Cancer Res. 2008; 14 (5): 1368–1376.
Chen F, Chen GK, Stram DO et al. A genome wide association study of breast cancer in women of African ancestry. Hum Genet 2013; 132:39–48.
Chen VW, Correa P, Kurman RJ et al. Histological characteristics of breast carcinoma in blacks and whites. Cancer Epidemiol Biomarkers Prev 1994; 3:127–135.
Chen X., He C., Han D., Zhou M., Wang Q., Tian J., Li L., Xu F., Zhou E., Yang K., “The predictive value of Ki-67 before neoadjuvant chemotherapy for breast cancer: a systematic review and meta-analysis,» Future Oncol. 10.2217/fon-2016-0420.
Denkert C, Budczies J, Von Minckwitz G, Wienert S, Loibl S, Klauschen F. Strategies for developing Ki-67 as a useful biomarker in breast cancer. Breast 2015; 24 (Suppl. 2), S67–72.
Denkert C, Loibl S, Müller BM et al. Ki-67 levels as predictive and prognostic parameters in pretherapeutic breast cancer core biopsies: a translational investigation in the neoadjuvant GeparTrio trial. Ann Oncol 2013; 24:2786-93.
Dowsett M, Nielsen TO, A’Hern R et al. Assessment of Ki-67 in breast cancer: recommendations from the International Ki-67 in Breast Cancer working group. J Natl Cancer Inst 2011; 103:1656-64.
Duchrow M, Schlüter 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 Ki-67. Cell Prolif 1996; 29:1-12.
Dumontet C, Krajewska M, Treilleux I et al. BCIRG 001 molecular analysis: prognostic factors in node-positive breast cancer patients receiving adjuvant chemotherapy. Clin Cancer Res 2010; 16:3988-97.
Eloy J. W., Hill H. A., Chen et al., “Racial differences in survival from breast cancer:results of the National Cancer Institute Black White Cancer Survival Study,” Journal of the American Medical Association 1994;vol. 272, no. 12 pp. 947-954.
Elston CW, Ellis IO: Pathological prognostic factors in breast cancer. I. The value of histological grade in breast cancer: Experience from a large study with long-term follow-up. Histopathology 2002; 41:154-161, suppl 3A.
Endl E. and Gerdes J., «The Ki-67 protein: fascinating forms and an unknown function,” Experimental Cell Research 2000; vol. 257, no. 2, pp. 231-237.
Esteva FJ, Sahin AA, Cristofanilli M, Coombes K, Lee SJ, et al. Prognostic role of a multigene reverse transcriptase-PCR assay in patients with node-negative breast cancer not receiving adjuvant systemic therapy. Clin Cancer Res 2005; 11: 3315–3319.
Fasching PA, Heusinger K, Haeberle L et al. Ki-67, chemotherapy response, and prognosis in breast cancer patients receiving neoadjuvant treatment. BMC Cancer 2011; 11, 486.
Ferlay, JSL; Ervik, M; Dikshit, R et Al. IARC. Globocan2012: estimated cancer incidence, mortality and prevalence worldwide: IARC, Lyon, France: internation Agency for research on cancer; 2013. http://glorian.iarc.fr/pages/fact_sheets Cancer. aspX ( accessed Fed1, 2014).
Galant C., Berliere M, Isabelle L, Marbaix E. Nouveautés dans les facteurs histopronostiques des cancers des seins. Elsevier. Imagerie de la femme 2010; 20, 9-17.
Ganiy O. A. Jnr. and Ganiyu A. R,. Epidemiology of Breast cancer in Europe and Africa Review Article, journal of cancer Epidemiology 2012; 5 pages.
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.
Goldhirsch A, Winer EP, Coates AS et al. Personalizing the treatment of women with early breast cancer: highlights of the St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2013. Ann Oncol 2013; 24:2206-23.
Gong P., Wang Y., Liu G., Zhang J., Wang Z., New Insight into Ki-67 Expression at the Invasive Front in Breas tCancer. PLoS ONE 2013: e54912.
Grana X. and Reddy E. P, «Cell cycle control in mammalian cells: role of cyclins, cyclin dependent kinases (CDKs), growth suppressor genes and cyclin-dependent kinase inhibitors (CKIs),” Oncogene 1995; vol. 11, no. 2, pp. 211-219.
Grim J, Jandik P, Slanska I et al. Low expression of NQO1 predicts pathological complete response to neoadjuvant chemotherapy in breast cancer patients treated with TAC regimen. Folia Biol. (Praha) 2012; 58 (5), 185–192.
Hafeez F (1), Neboori HJ, Harigopal M, Wu H, Haffty BG, Yang Q, Schiff D, Moran MS. Is Ki-67 expression prognostic for local relapse in early-stage breast cancer patients treated with breast conservation therapy (BCT)?. Int J Radiat Oncol Biol Phys. 2013 Oct 1; 87 (2):344-8.
Heudel P., «Les nouveaux marqueurs pronostiques (Ki-67, micrométastases, génomique),” Francophones d’oncologie médicale, 2013.
Hickey M., Peate M.,. Saunders C. M, and Friedlander M., «Breast cancer in young women and its impact on reproductive function,” Human Reproduction Update 2009; Vol. 15, No. 3 pp. 323–339.
Hirata B. K. B, Oda J. M. M, Guembarovski R. L, Ariza B. C, Coral de Oliveira C. E, and Watanabe M. A. E., «Molecular Markers for Breast Cancer: Prediction on Tumor Behavior,» Disease Markers 2014; 12pages.
Hu Z, Fan C, Oh DS, et al. The molecular portraits of breast tumors are conserved across microarray platforms. BMC Genomics 2006; 7: 96.
Ingolf J-B., Russalina M., Simona M., Julia R., Gilda S., Bohle RM., Andrea H., Erich S., and Daniel H., «Can Ki-67 Play a Role in Prediction of Breast Cancer Patients`Response to Neoadjuvant Chemotherapy?,” BioMed Research International 2014.
Jin S, Kim SB, Ahn JH et al. 18 F-fluorodeoxyglucose uptake predicts pathological complete response after neoadjuvant chemotherapy for breast cancer: a retrospective cohort study. J. Surg. Oncol 2013; 107 (2), 180–187.
Jones RL, Salter J, A’Hern R, et al. Relationship between oestrogen receptor status and proliferation in predicting response and long-term outcome to neoadjuvant chemotherapy for breast cancer. Breast Cancer Res Treat. 2010; 119 (2):315–323.
Kashiwagi S., Yashiro M., Takashima T., Aomatsu N., Ikeda K., Ogawa Y., Ishikawa T., and Hirakawa K., «Advantages of adjuvant chemotherapy for patients with triple-negative breast cancer at Stage II: usefulness of prognostic markers E-cadherin and Ki-67,». Breast Cancer Research2011; 13:R122.
Lakhani S. R., Ellis I. O., Schnitt S. J., Tan M, Van de Vijver M. J. Who classification of tumours of the breast. International Agency for Research on cancer, Lyon 2012; pp 8, 20.
Luporsi E, André F, Spyratos F et al. Ki-67: level of evidence and methodological considerations for its role in the clinical management of breastcancer: analytical and critical review. Breast Cancer Res. Treat. 2012; 132 (3), 895–915.
Marcom PK, Isaacs C, Harris L, et al. The combination of letrozole and trastuzumab as first or second-line biological therapy produces durable responses in a subset of HER2 positive and ER positive advanced breast cancers. Breast Cancer Res Treat. 2007; 102 (1 ): 43–49.
Millikan RC, Newman B, Tse CK et al. Epidemiology of basal-like breast cancer. Breast Cancer ResTreat 2008; 109:123–139.
Morris GJ, Mitchell EP. Higher incidence of aggressive breast cancers in African-American women: A review. J Natl Med Assoc 2008; 100:698–702.
Munakata S, Hendricks JB. Effect of fixation time and microwave oven heating time on retrieval of the Ki-67 antigen from paraffin-embedded tissue. J Histochem Cytochem. 1993; 41 (8):1241–1246.
O’Brien KM, Cole SR, Tse CK et al. Intrinsic breast tumor subtypes, race, and long-termsurvival in the Carolina Breast Cancer Study. Clin Cancer Res 2010; 16:6100–6110.
Oh DS, Troester MA, Usary J, et al. Estrogen-regulated genes predict survival in hormone receptor-positive breast cancers. J Clin Oncol 2006; 24 (11): 1656–1664.
Penault-Llorca F, Abrial C, Raoelfils I et al. Changes and predictive and prognostic value of the mitotic index, Ki-67, cyclin D1, and cyclo-oxygenase-2 in 710 operable breast cancer patients treated with neoadjuvant chemotherapy. Oncologist 2008; 13 (12), 1235–1245.
Penault-Llorca F, Andre F, Sagan C, et al. Ki-67 expression and docetaxel efficacy in patients with estrogen receptor-positive breast cancer. J Clin Oncol. 2009; 27 (17):2809–2815.
Penault-Llorca F., Bayol B., Radosevic-Robin N., «L’évaluation de Ki-67 dans le cancer du sein:actualités (Ki-67 assessment in breast cancer: an update),» Prolifération et cycle cellulaire, 2017; Vol. VI - n° 1 - janvier-février-mars.
Peppercorn J, Perou CM, Carey LA. Molecular subtypes in breast cancer evaluation and management: Divide and conquer. Cancer Invest 2008; 26: 1–10.
Perou CM, Jeffrey SS, van de Rijn M, et al. Distinctive gene expression patterns in human mammary epithelial cells and breast cancers. Proc Natl Acad Sci USA. 1999; 96 (16): 9212–9217.
Pinhel IF, Macneill FA, Hills MJ, et al. Extreme loss of immunoreactive p-Akt and p-Erk1/2 during routine fixation of primary breast cancer. Breast Cancer Res. 2010; 12 (5):R76.
Porter P. L, Lund M. J, Lin M. G et al., «Racial differences in the expression of cell cycle-regulatory proteins in breast carcinoma: study of young African American and white women in Atlanta, Georgia,” Cancer 2004; Vol. 100, no. 12, pp. 2533-2542.
Romero Q, Pär-Ola Bendahl, Mårten Fernö, Dorthe Grabau and Signe Borgquist, «A novel model for Ki-67 Assessment in breast cancer” Romero et al. Diagnostic pathology 2014; 9:118.
Ross JS, Linette GP, Stec J, Clark E, Ayers M, Leschly N, Symmans WF, Hortobagyi GN, Pusztai L:Breast cancer biomarkers and molecular medicine. Expert Rev Mol Diagn2003; 3:573–585.
Royston P., Altman D. G, and Sauerbrei W., «Dichotomizing continuous predictors in multiple regression: a bad idea,” Statistics in Medecine 2006; vol. 25, no. 1, pp. 127-141.
Schmidt M., Fashing P. A., Beckmann M. W., and Kolbl H., «Biomarkers in breast cancer-an update,” Geburtsh Frauenheilk 2012; vol. 72, no. 9, pp. 819-832.
Sherr C. J, «G1 phase progression: cycling on cue,” cell 1994; vol. 79, no. 4, pp. 551-555.
Silber JH, Rosenbaum PR, Clark AS, Giantonio BJ, Ross RN, Teng Y, Wany M, Niknam BA, Ludwig JM, Wang W, Even-Shoshan O, Fox KR, characteristics associated with differences in survival among black and white women whith breast cancer. JAMA. 2013 Jul 24; 310 (4):389-97.
Stratton M. R, Campell P. J and Futreal A. The cancer genome: review, Nature 2009 April; 458, 719-724.
Tan QX, Qin QH, Yang WP, Mo QG, Wei CY. Prognostic value of Ki-67 expression in HR-negative breast cancer before and after neoadjuvant chemotherapy. Int. J. Clin. Exp. Pathol. 2014; 7 (10), 6862–6870.
Tea MK, Fan L, Delancey JW, Staudigl C, Steurer S, Lang C, Shao Z M, Singer CF, “Is breast cancer in young asian women more aggressive than in caucasians ?A cross-sectional analysis,”Tumour Biol. 2013 Aug; 34 (4):2379-82.
Urruticoechea A., Smith I. E, and Dowsett M., «Proliferation marker Ki-67 in early breast cancer,” Journal of Clinical oncology 2005; vol. 23, no. 28, pp. 7212-7220.
Van Diest PJ, van der Wall E, Baak JP:Prognostic value of proliferation in invasive breast cancer: a review. J Clin Pathol2004; 57:675–681.
Varga Z, Diebold J, Dommann-Scherrer C, Frick H, Kaup D, et al. How reliable is Ki-67 immunohistochemistry in grade 2 breast carcinomas? A QA study of the Swiss Working Group of Breast- and Gynecopathologists. PLoS One2012; 7: e37379.
Viale G:Pathological work up of the primary tumor: getting the proper information out of it. Breast2011; 20 (Suppl 3):S82–S86.
Visscher DW, Wallis T, Jimenez RE. Centrally necrosing carcinoma: a distinctive histologic subtype of breast cancer with an aggressive clinical behavior. Mod Pathol 2000; 13:49A.
Wildiers H, Brain EG. Adjuvant chemotherapy in elderly patients with breast cancer: Where are we? Curr Opin Oncol 2005; 17:566–572.
Wittekind Ch., Asamura H., Sobin L. H. TNM Atlas, Sixth Edition. Union for international Cancer control2014; 231, 232.
Wojnar A, Pula B, Piotrowska A, Jethon A, Kujawa K, et al. Correlation of intensity of MT-I/II expression with Ki-67 and MCM-2 proteins in invasive ductal breast carcinoma. Anticancer Res2011; 31: 3027–3033.
Wu Y., Luo H., Kanaan N., and Wu J., «the proteasome controls the expression of proliferation-associated nuclear antigen Ki-67,” Journal of Cellular Biochemistry2000; vol. 76, no. 4, pp. 596-604.
Xue C., Wang X, Peng R., Shi Y., Qin T., Liu D., Teng X., Wang S., Zhang L,. and Yuan., Z., «Distribution, clinicopathologic features and survival of breast cancer subtypes in Southern China,» Cancer Sci, September 2012, vol. 103 no. 9 1679–1687.
Yerushalmi R, Woods R, Ravdin PM, Hayes MM, Gelmon KA. Ki-67 in breast cancer: prognostic and predictive potential. Lancet Oncol. 2010; 11 (2), 174–183).
Yoshioka T, Hosoda M, Yamamoto M et al. Prognostic significance of pathologic complete response and Ki-67 expression after neoadjuvant chemotherapy in breast cancer. Breast Cancer2015; 22 (2), 185–191.