Kaiso Expression in Triple Negative Breast Cancer in a Tertiary Hospital in Ghana

Main Article Content

Babatunde Duduyemi
Thelma Kwakye
Lorraine Sallah


Kaiso expression, TNBC, Tissue microarray, Immunohistochemistry


Background: Breast cancer has produced more lost disability-adjusted life years (DALYs) than any other type of cancer. The prevalence of the disease, especially triple negative breast cancer (TNBC) in Africa is on the rise, with poor survival rates. With the great advancements in treatments of breast cancers, that of TNBC is still a challenge due to its narrowed treatment options and poor disease prognosis. This research seeks to explore the expression of kaiso in Ghanaian breast cancer and how they may modulate clinicopathological features, and disease prognosis.

Methodology: A cross sectional and retrospective study was conducted on formalin-fixed paraffin-embedded (FFPE) breast cancer tissues retrieved from the archives of the pathology unit of Komfo Anokye Teaching Hospital (KATH). Immunohistochemistry assessment was performed on haematoxylin and eosin-stained slides selected for tissue microarray construction. Data were analysed using SPSS version 28 and Microsoft excel 2013.

Result: 55.3% of the cases tested negative to progesterone receptor (PR), oestrogen receptor (ER), and human epidermal growth receptor 2 (HER2). There were significant associations between menopausal status and molecular subtype (p=0.010), Kaiso expression and histological diagnoses (<0.001) and Kaiso against lymphovascular invasion (0.050). However, there were no significant associations between Kaiso localization and the clinicopathological features although 63.9% of the expression was seen in the nucleus.

Conclusion: The study indicates that Kaiso is highly expressed in Ghanaian TNBC and likely associated with worse outcomes in aggressive tumour types.

Abstract 25 | PDF Downloads 52 EPUB Downloads 11


1. Kalimuthu R, Yegiyants SS, Brenzek C. Anatomy of the Breast, Axilla, and Chest Wall. In: Breast disease: Comprehensive management. 2015. p. 1–22.

2. Corradini S, Reitz D, Pazos M, Schönecker S, Braun M, Harbeck N, et al. Mastectomy or Breast-Conserving Therapy for Early Breast Cancer in Real-life Clinical Practice: Outcome Comparison of 7565 cases. Cancers (Basel). 2019;11(2).

3. Al –Gaithy ZK, Yaghmoor BE, Koumu MI, Alshehri KA, Saqah AA, Alshehri HZ. Trends of mastectomy and breast-conserving surgery and related factors in female breast cancer patients treated at King Abdulaziz University Hospital, Jeddah, Saudi Arabia, 2009–2017: A retrospective cohort study. Ann Med Surg 2019;41:47–52. https://doi.org/10.1016/j.amsu.2019.03.012

4. Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;0(0):1–41.

5. Atta Manu E, Bedu-Addo K, Titiloye NA, Ameh-Mensah C, Opoku F, Duduyemi BM. Expression of Tumour-Associated MUC1 Is a Poor Prognostic Marker in Breast Cancer in Kumasi, Ghana. J Oncol. 2020;2020:1–7.

6. Thomas AS, Kidwell KM, Oppong JK, Adjei EK, Osei-Bonsu E, Boahene A, et al. Breast Cancer in Ghana: Demonstrating the Need for Population-Based Cancer Registries in Low- and Middle-Income Countries. J Glob Oncol. 2017;3(6):765–72.

7. Galukande M, Wabinga H, Mirembe F, Karamagi C, Asea A. Molecular breast cancer subtypes prevalence in an indigenous Sub Saharan African population. Pan Afr Med J. 2014 Apr 5;17:249. doi: 10.11604/pamj.2014.17.249.330.

8. Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, et al. Cancer incidence and mortality worldwide: Sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2015;136(5):E359–86.

9. Brinton L, Figueroa J, Adjei E, Ansong D, Biritwum R, Edusei L, et al. Factors contributing to delays in diagnosis of breast cancers in Ghana, West Africa. Breast Cancer Res Treat. 2017;162(1):105–14.

10. Aziato L, Clegg-Lamptey JNA. Breast Cancer Diagnosis and Factors Influencing Treatment Decisions in Ghana. Health Care Women Int. 2015;36(5):543–57.

11. Anyigba CA, Awandare GA, Paemka L. Breast cancer in sub-Saharan Africa: The current state and uncertain future. Exp Biol Med. 2021;246(12):1377–87.

12. Titiloye NA, Foster A, Omoniyi-Esan GO, Komolafe AO, Daramola AO, Adeoye OA, et al. Histological Features and Tissue Microarray Taxonomy of Nigerian Breast Cancer Reveal Predominance of the High-Grade Triple-Negative Phenotype. Pathobiology. 2016;83(1):24–32.

13. Titiloye N, Omoniyi-Esan G, Adisa A, Komolafe A, Afolabi O, Adelusola K. Breast cancer in a Nigerian cohort : histopathology , immunohistochemical profile and survival. Postgrad Med J Ghana. 2013;2(2):83–7.

14. Bassey-Archibong BI, Hercules SM, Rayner LGA, Skeete DHA, Smith Connell SP, Brain I, et al. Kaiso is highly expressed in TNBC tissues of women of African ancestry compared to Caucasian women. Cancer Causes Control. 2017;28(11):1295–304.

15. Agboola AOJ, Banjo AAF, Anunobi C, Salami B, Deji-Agboola M, Musa A, et al. Helix-loop-helix protein inhibitor of differentiation 4 (ID4) expression is an indicator of poor survival in Nigerian breast cancer women. J Africain du Cancer / African J Cancer. 2014;6(3):129–37.

16. Ohene-Yeboah M, Adjei E. Breast cancer in Kumasi, Ghana. Ghana Med J. 2012;46(1):8–13.

17. Carey L, Winer E, Viale G, Cameron D, Gianni L. Triple-negative breast cancer: Disease entity or title of convenience? Nat Rev Clin Oncol 2010;7(12):683–92.http://dx.doi.org/10.1038/nrclinonc.2010.154

18. Kwiecien JM, Bassey-Archibong BI, Dabrowski W, Rayner LG, Lucas AR, Daniel JM. Loss of Kaiso expression in breast cancer cells prevents intra-vascular invasion in the lung and secondary metastasis. PLoS One. 2017;12(9):1–17.

19. Vermeulen JF, van de Ven RAH, Ercan C, van der Groep P, van der Wall E, Bult P, et al. Nuclear Kaiso expression is associated with high grade and triple-negative invasive breast cancer. PLoS One. 2012;7(5).

20. Bassey-Archibong BI, Kwiecien JM, Milosavljevic SB, Hallett RM, Rayner LGA, Erb MJ, et al. Kaiso depletion attenuates transforming growth factor-β signaling and metastatic activity of triple-negative breast cancer cells. Oncogenesis. 2016;5(3).

21. Wang L, Ma J, Wang X, Peng F, Chen X, Zheng B, et al. Kaiso (ZBTB33) Downregulation by Mirna-181a Inhibits Cell Proliferation, Invasion, and the Epithelial-Mesenchymal Transition in Glioma Cells. Cell Physiol Biochem. 2018;48(3):947–58.

22. Robinson SC, Klobucar K, Pierre CC, Ansari A, Zhenilo S, Prokhortchouk E, et al. Kaiso differentially regulates components of the Notch signaling pathway in intestinal cells. Cell Commun Signal. 2017;15(1):1–13.

23. Shankar E, Gupta K, Gupta S. Dietary and Lifestyle Factors in Epigenetic Regulation of Cancer. Epigenetics of Cancer Prevention. 2018:361–394.http://dx.doi.org/10.1016/B978-0-12-812494-9.00017-2

24. Bettegowda C, Sausen M, Leary RJ, Kinde I, Wang Y, Agrawal N, et al. Detection of circulating tumor DNA in early- and late-stage human malignancies. Sci Transl Med. 2014;6(224).

25. Zhang H, Moisini I, Ajabnoor RM, Turner BM, Hicks DG. Applying the New Guidelines of HER2 Testing in Breast Cancer. Curr Oncol Rep. 2020;22(5).

26. Allison KH, Hammond MEH, Dowsett M, McKernin SE, Carey LA, Fitzgibbons PL, et al. Estrogen and progesterone receptor testing in breast cancer: American society of clinical oncology/college of American pathologists guideline update. Arch Pathol Lab Med. 2020;144(5):545–63.

27. Sinn HP, Kreipe H. A brief overview of the WHO classification of breast tumors, 4th edition, focusing on issues and updates from the 3rd edition. Breast Care. 2013;8(2):149–54.

28. Cadoo KA, Traina TA, King TA. Advances in Molecular and Clinical Subtyping of Breast Cancer and Their Implications for Therapy. Surg Oncol Clin N Am. 2013;22:823–40.

29. Pitt JJ, Riester M, Zheng Y, Yoshimatsu TF, Sanni A, Oluwasola O, et al. Characterization of Nigerian breast cancer reveals prevalent homologous recombination deficiency and aggressive molecular features. Nat Commun. 2018;9(1):4181.

30. Bassey-Archibong B. Unravelling the biological roles of Kaiso in triple negative breast cancers. Macsphere:Macmaster Universities Libraries Institutional Repository: Open Access dissertations and theses Nov 2017. https://macsphere.mcmaster.ca/handle/11375/22033

31. Mensah AC, Yarney J, Nokoe SK, Opoku S, CleggLamptey JN. Survival Outcomes of Breast Cancer in Ghana: An Analysis of Clinicopathological Features. Open Access Libr J. 2016;3(e2145):1–11.

32. Seshie B, Adu-aryee NA, Dedey F, Calys-tagoe B. A retrospective analysis of breast cancer subtype based on ER / PR and HER2 status in Ghanaian patients at the Korle Bu Teaching Hospital , Ghana. BMC Clin Pathol 2015;1–8.http://dx.doi.org/10.1186/s12907-015-0014-4

33. Usman A, Iliyasu Y, Atanda AT. Molecular Subtyping of Carcinoma of the Female Breast in a Tertiary Teaching Hospital in Northern Nigeria. Ann Trop Pathol. 2019;10(1):20–6.

34. Cherbal F, Gaceb H, Mehemmai C, Saiah I, Bakour R, Rouis AO, et al. Distribution of molecular breast cancer subtypes among Algerian women and correlation with clinical and tumor characteristics: A population-based study. Breast Dis. 2015;35(2):95–102.

35. Hadgu E, Seifu D, Tigneh W, Bokretsion Y, Bekele A, Abebe M, et al. Breast cancer in Ethiopia: evidence for geographic difference in the distribution of molecular subtypes in Africa. BMC Womens Health. 2018 Dec;18(1):40.

36. Wang C, Kar S, Lai X, Cai W, Arfuso F, Sethi G, et al. Triple negative breast cancer in Asia: An insider’s view. Cancer Treat Rev 2018;62:29–38. https://doi.org/10.1016/j.ctrv.2017.10.014

37. Zugazagoitia J, Guedes C, Ponce S, Ferrer I, Molina-Pinelo S, Paz-Ares L. Current Challenges in Cancer Treatment. Clin Ther 2016;38(7):1551–66. http://dx.doi.org/10.1016/j.clinthera.2016.03.026

38. Ameh-Mensah C, Duduyemi BM, Bedu-Addo K, Atta Manu E, Opoku F, Titiloye N. The Analysis of bcl-2 in Association with p53 and Ki-67 in Triple Negative Breast Cancer and Other Molecular Subtypes in Ghana. J Oncol. 2021; 7054134. doi: 10.1155/2021/7054134.

39. Muthoni A, Miller AN. An Exploration of rural and urban Kenyan women’s knowledge and attitudes regarding breast cancer and breast cancer early detection measures. Health Care Women Int. 2010;31(9):801–16.

40. Quayson SE, Wiredu EK, Adjei DN, Anim JT. Breast cancer in Accra , Ghana. J Med Biomed Sci. 2014;3(3):21–6.

41. Kohler R, Moses A, Krysiak R, Liomba N, Gopal S. Pathologically confirmed breast cancer in Malawi: a descriptive study: Clinical profile of breast cancer. Malawi Med J. 2015 Apr;27(1): 27(1):10-2. doi: 10.4314/mmj.v27i1.3.

42. Bleil ME, Booth-LaForce C, Benner AD. Race Disparities in Pubertal Timing: Implications for Cardiovascular Disease Risk Among African American Women. Popul Res Policy Rev. 2017;36(5):717–38.

43. Forae G, Nwachokor F, Igbe A. Histopathological profile of breast cancer in an African population. Ann Med Health Sci Res. 2014;4(3):369.

44. Yábar A, Meléndez R, Muñoz S, Deneo H, Freire J, Domínguez V, et al. Effect of Ki-67 assessment in the distribution of breast cancer subtypes: Evaluation in a cohort of Latin American patients. Mol Clin Oncol. 2017;6(4):503–9.

45. Di Sibio A, Abriata G, Forman D, Sierra MS. Female breast cancer in Central and South America. Cancer Epidemiol 2016;44:S110–20.http://dx.doi.org/10.1016/j.canep.2016.08.010

46. Ryu YJ, Kang SJ, Cho JS, Yoon JH, Park MH. Lymphovascular invasion can be better than pathologic complete response to predict prognosis in breast cancer treated with neoadjuvant chemotherapy. Med (United States). 2018;97(30).

47. Pierre CC, Hercules SM, Yates C, Daniel JM. Dancing from bottoms up – Roles of the POZ-ZF transcription factor Kaiso in Cancer. Biochim Biophys Acta - Rev Cancer 2019;1871(1):64–74.

48. Jones J, Wang H, Karanam B, Theodore S, Dean-Colomb W, Welch DR, Grizzle W, Yates C. Nuclear localization of Kaiso promotes the poorly differentiated phenotype and EMT in infiltrating ductal carcinomas. Clin Exp Metastasis 2014;31(5):497-510. doi: 10.1007/s10585-014-9644-7.