Ki-67 expression and its correlation with clinicopathological parameters in Iraqi breast cancer patients

Ammar A Hussein; Rayah S Baban; Qahtan A Mahdi; Zuhair M Hussein; Areege M Kamal

doi:10.53730/ijhs.v8n2.14994

Authors

Ammar A. Hussein
ammar.a@uodiyala.edu.iq
University of Diyala, 32001, Ba’aqubah, Diyala, Iraq
Rayah S. Baban Al-Nahrain University, Baghdad, Iraq
Qahtan A. Mahdi Al-Nahrain University, Baghdad, Iraq
Zuhair M. Hussein University of Diyala, 32001, Ba’aqubah, Diyala, Iraq
Areege M. Kamal Oncology Teaching Hospital, Medical City, Babalmuadum, Baghdad, Iraq

Keywords:

benign tumor, breast cancer, immunohistochemical expression, Ki-67, prognostic biomarker

Abstract

Breast cancer is the most common cancer worldwide and the major cause of cancer-related death among women in both developed and developing countries. In Iraq, breast cancer accounted for 37.9% of all malignant cases in 2020 and 15.3% of cancer-related fatalities. Relevant biomarkers play an important role in predicting prognosis and deciding the most effective therapy for each patient to delay metastases and reduce mortality. Objective: This study aimed to assess the significance of Ki-67 expression as a prognostic biomarker in breast cancer patients as well as investigate the correlations between Ki-67 and their clinicopathological features. Methods: The case-control study comprised sixty newly diagnosed breast cancer patients and ten women with benign breast tumors who served as controls. We assessed the tissue expression level of Ki-67 protein using the immunohistochemistry technique. Results: Our results showed that the median immunohistochemical expression scores of Ki-67 in the newly diagnosed breast cancer group were higher than those of the control group; the difference was significant (p < 0.001). The Ki-67 expression score in breast cancer cells increases with tumor size and grade. Ki-67 expression showed a substantial negative correlation with estrogen receptor expression and a significant positive correlation with HER2 expression.

Downloads

Download data is not yet available.

References

Abele, N., Tiemann, K., Krech, T., Wellmann, A., Schaaf, C., Länger, F., ... & Lang, T. (2023). Noninferiority of Artificial Intelligence–Assisted Analysis of Ki-67 and Estrogen/Progesterone Receptor in Breast Cancer Routine Diagnostics. Modern Pathology, 36(3), 100033. https://doi.org/10.1016/j.modpat.2022.100033

Ács, B., Zámbó, V., Vízkeleti, L., Szász, A. M., Madaras, L., Szentmártoni, G., ... & Tőkés, A. M. (2017). Ki-67 as a controversial predictive and prognostic marker in breast cancer patients treated with neoadjuvant chemotherapy. Diagnostic pathology, 12, 1-12.

Afkari, H., Makrufardi, F., Hidayat, B., Budiawan, H., & Kartamihardja, A. H. S. (2021). Correlation between ER, PR, HER-2, and Ki-67 with the risk of bone metastases detected by bone scintigraphy in breast cancer patients: A cross sectional study. Annals of Medicine and Surgery, 67, 102532. https://doi.org/10.1016/j.amsu.2021.102532

Ahmed, S. T., Ahmed, A. M., Musa, D. H., Sulayvani, F. K., Al-Khyatt, M., & Pity, I. S. (2018). Proliferative index (Ki67) for prediction in breast duct carcinomas. Asian Pacific journal of cancer prevention: APJCP, 19(4), 955.

Al-Nuaimi, H. A. A., Hamdi, E., & Mohammed, B. B. (2020). Ki-67 Expression in Breast Cancer, Its Correlation with ER, PR and Other Prognostic Factors in Nineveh Province. Annals of the college of medicine, Mosul, 42(1), 1-10.

Aman, N. A., Doukoure, B., Koffi, K. D., Koui, B. S., Traore, Z. C., Kouyate, M., ... & Effi, A. B. (2019). Immunohistochemical evaluation of Ki-67 and comparison with clinicopathologic factors in breast carcinomas. Asian Pacific journal of cancer prevention: APJCP, 20(1), 73-79.

Barboro, P., Rubagotti, A., Poddine, S., Grillo, F., Mastracci, L., & Boccardo, F. (2022). The prognostic value of aspartate beta-hydroxylase in early breast cancer. The International Journal of Biological Markers, 37(3), 328-335.

Begum, M., Karim, S., Malik, A., Khurshid, R., Asif, M., Salim, A., ... & Abuzenadah, A. M. (2012). CA 15-3 (Mucin-1) and physiological characteristics of breast cancer from Lahore, Pakistan. Asian Pacific Journal of Cancer Prevention, 13(10), 5257–5261.

Booth, D. G., & Earnshaw, W. C. (2017). Ki-67 and the chromosome periphery compartment in mitosis. Trends in Cell Biology, 27(12), 906-916.

Cianfrocca, M., & Goldstein, L. J. (2004). Prognostic and predictive factors in early-stage breast cancer. The oncologist, 9(6), 606-616.

Davey, M. G., Hynes, S. O., Kerin, M. J., Miller, N., & Lowery, A. J. (2021). Ki-67 as a prognostic biomarker in invasive breast cancer. Cancers, 13(17), 4455.

Goldhirsch, A., Wood, W. C., Coates, A. S., Gelber, R. D., Thürlimann, B., & Senn, H. J. (2011). 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. Annals of oncology, 22(8), 1736-1747. https://doi.org/10.1093/annonc/mdr304

Hashmi, A. A., Hashmi, K. A., Irfan, M., Khan, S. M., Edhi, M. M., Ali, J. P., ... & Khan, A. (2019). Ki67 index in intrinsic breast cancer subtypes and its association with prognostic parameters. BMC research notes, 12, 1-5.

Hussein, A. A., Baban, R. S., & Mahdi, Q. A. (2022). Evaluation of Thymidine Kinase-1 as a potential biomarker and its association with CA 15-3 in patients with non-metastatic breast cancer. NeuroQuantology, 20(6), 5943.

Hussein, A. A., Baban, R. S., & Mahdi, Q. A. (2022). Evaluation of aromatase as a potential biomarker and its association with CA 15-3 in patients with non-metastatic breast cancer. International Journal of Health Sciences, 6(S5), 8339–8349. https://doi.org/10.53730/ijhs.v6nS5.10552

Iqbal, A., Tamgadge, S., Tamgadge, A., Pereira, T., Kumar, S., Acharya, S., & Jadhav, A. (2020). Evaluation of Ki-67 expression in oral submucous fibrosis and its correlation with clinical and histopathological features. Journal of Microscopy and Ultrastructure, 8(1), 20-24.

Jakobsen, J. N., & Sørensen, J. B. (2013). Clinical impact of ki-67 labeling index in non-small cell lung cancer. Lung cancer, 79(1), 1-7. https://doi.org/10.1016/j.lungcan.2012.10.008

Janssen, J., Oevermann, A., Walter, I., Tichy, A., Kummer, S., & Gradner, G. (2023). Osteopontin and Ki-67 expression in World Health Organization graded canine meningioma. Journal of comparative pathology, 201, 41-48. https://doi.org/10.1016/j.jcpa.2022.12.011

Kamranzadeh, H., Ardekani, R. M., Kasaeian, A., Sadighi, S., Maghsudi, S., Jahanzad, I., & Maleki, N. (2019). Association between Ki-67 expression and clinicopathological features in prognosis of breast cancer: A retrospective cohort study. Journal of Research in Medical Sciences, 24(1), 30.

Maranta, A. F., Broder, S., Fritzsche, C., Knauer, M., Thürlimann, B., Jochum, W., & Ruhstaller, T. (2020). Do YOU know the Ki-67 index of your breast cancer patients? Knowledge of your institution’s Ki-67 index distribution and its robustness is essential for decision-making in early breast cancer. The Breast, 51, 120-126. https://doi.org/10.1016/j.breast.2020.03.005

Martino, F., Ilardi, G., Varricchio, S., Russo, D., Di Crescenzo, R. M., Staibano, S., & Merolla, F. (2024). A deep learning model to predict Ki-67 positivity in oral squamous cell carcinoma. Journal of Pathology Informatics, 15. https://doi.org/10.1016/j.jpi.2023.100354

Miller, I., Min, M., Yang, C., Tian, C., Gookin, S., Carter, D., & Spencer, S. L. (2018). Ki67 is a graded rather than a binary marker of proliferation versus quiescence. Cell reports, 24(5), 1105-1112.

Noske, A., Anders, S. I., Ettl, J., Hapfelmeier, A., Steiger, K., Specht, K., Weichert, W., Kiechle, M., & Klein, E. (2020). Risk stratification in luminal-type breast cancer: Comparison of Ki-67 with EndoPredict test results. Breast, 49, 101–107. https://doi.org/10.1016/j.breast.2019.11.004

Ortiz-Abellán, C., Aguado-Sarrió, E., Prats-Montalbán, J. M., Camps-Herrero, J., & Ferrer, A. (2024). New breast cancer biomarkers from diffusion magnetic resonance imaging based on the Diffusion Tensor using multivariate curve resolution (MCR) models. Chemometrics and Intelligent Laboratory Systems, 251. https://doi.org/10.1016/j.chemolab.2024.105171

Ragab, H. M., Samy, N., Afify, M., Abd El Maksoud, N., & Shaaban, H. M. (2018). Assessment of Ki-67 as a potential biomarker in patients with breast cancer. Journal of Genetic Engineering and Biotechnology, 16(2), 479-484. https://doi.org/10.1016/j.jgeb.2018.03.002

Sobecki, M., Mrouj, K., Camasses, A., Parisis, N., Nicolas, E., Lleres, D., ... & Fisher, D. (2016). The cell proliferation antigen Ki-67 organises heterochromatin. elife, 5, e13722.

Sun, X., & Kaufman, P. D. (2018). Ki-67: more than a proliferation marker. Chromosoma, 127, 175-186.

Sung, H., Ferlay, J., Siegel, R. L., Laversanne, M., Soerjomataram, I., Jemal, A., & Bray, F. (2021). Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: a cancer journal for clinicians, 71(3), 209-249.

Tarighati, E., Keivan, H., & Mahani, H. (2023). A review of prognostic and predictive biomarkers in breast cancer. Clinical and experimental medicine, 23(1), 1-16.

Torlakovic, E. E., Baniak, N., Barnes, P. J., Chancey, K., Chen, L., Cheung, C., Clairefond, S., Cutz, J. C., Faragalla, H., Gravel, D. H., Dakin Hache, K., Iyengar, P., Komel, M., Kos, Z., Lacroix-Triki, M., Marolt, M. J., Mrkonjic, M., Mulligan, A. M., Nofech-Mozes, S., … Bigras, G. (2024). Fit-for-Purpose Ki-67 Immunohistochemistry Assays for Breast Cancer. Laboratory Investigation, 104(7). https://doi.org/10.1016/j.labinv.2024.102076

Uxa, S., Castillo-Binder, P., Kohler, R., Stangner, K., Müller, G. A., & Engeland, K. (2021). Ki-67 gene expression. Cell Death & Differentiation, 28(12), 3357-3370.

Viale, G., Hanlon Newell, A. E., Walker, E., Harlow, G., Bai, I., Russo, L., ... & Maisonneuve, P. (2019). Ki-67 (30-9) scoring and differentiation of Luminal A-and Luminal B-like breast cancer subtypes. Breast Cancer Research and Treatment, 178, 451-458.

Wang, J. P., Liu, L., Li, Z. A., Wang, Q., Wang, X. Y., & Lin, J. (2021). Ki-67 labelling index is related to the risk classification and prognosis of gastrointestinal stromal tumours: a retrospective study. Gastroenterologia y hepatologia, 44(2), 103–114. https://doi.org/10.1016/j.gastrohep.2020.05.022

World Health Organization (WHO) and the International Agency for Research on Cancer (IARC) (2020). Iraqi Cancer incidence and mortality, Iraq - Global Cancer Observatory. Globocan 2020, pp. 2020–2021.

Wu, Q., Ma, G., Deng, Y., Luo, W., Zhao, Y., Li, W., & Zhou, Q. (2019). Prognostic value of Ki-67 in patients with resected triple-negative breast cancer: a meta-analysis. Frontiers in oncology, 9, 1068.

Wu, Y., Ma, Q., Fan, L., Wu, S., & Wang, J. (2024). An Automated Breast Volume Scanner-Based Intra- and Peritumoral Radiomics Nomogram for the Preoperative Prediction of Expression of Ki-67 in Breast Malignancy. Academic Radiology, 31(1), 93–103. https://doi.org/10.1016/j.acra.2023.07.004

Yerushalmi, R., Woods, R., Ravdin, P. M., Hayes, M. M., & Gelmon, K. A. (2010). Ki67 in breast cancer: prognostic and predictive potential. The lancet oncology, 11(2), 174-183.

Zeng, M., Zhou, J., Wen, L., Zhu, Y., Luo, Y., & Wang, W. (2021). The relationship between the expression of Ki-67 and the prognosis of osteosarcoma. BMC cancer, 21, 1-9.

Zhou, L., Ning, D., Gou, L., Liang, Y., & Yu, J. (2024). Study on the correlation between different expression levels of Ki-67 and ultrasonic image characteristics in primary breast lymphoma. Journal of Radiation Research and Applied Sciences, 17(1), 100820. https://doi.org/10.1016/j.jrras.2024.100820

Zhu, X., Chen, L., Huang, B., Wang, Y., Ji, L., Wu, J., ... & Wang, Z. (2020). The prognostic and predictive potential of Ki-67 in triple-negative breast cancer. Scientific reports, 10(1), 225.