Published: 2019-05-29

Comparison of diagnostic validity between mitotic activity index and Ki-67 expression as predictor for breast cancer in distant metastasis

Andreasta Ginting, I. Gede Budhi Setiawan, I. Wayan Sudarsa, I. Gede Raka Widiana


Background: One particular cause of death from breast cancer is distant metastasis. In this study, we calculate and compare  diagnostic value of Mitotic Activity Index (MAI) and Ki-67 expression in predicting distant metastasis.

Methods: Study was conducted in Sanglah Hospital from January 2017 to February 2019. All histopathology results from open biopsy are examined, thus MAI and Ki-67 values were obtained. We divided this into 2 groups: MAI high (≥20/HPF), low (<20/HPF) and Ki-67 high (≥20%) and low (<20%). We compared with distant metastasis event as gold standard, obtained from radiology examination. We count all diagnostic characteristics (sensitivity, specificity, positive and negative predictive value, accuracy, and likelihood ratio). We compared these diagnostic validities from data area under curve (AUC) with p value <0.005 considered to be statistically significant.

Results: A total of 173 breast cancer patients were participated in this study, 92 of them had distant metastasis (53.2%) and 81 patients didn’t have any distant metastasis (46.8%). MAI had relative high specificity (82.7%) and Ki-67 had fair sensitivity values (69.6%). There are 0.08 point AUC differences between these two variables. With p value higher than 0.05 (0.06), it can be summarized that these two variables are not different significantly and statistically.

Conclusions: There is not any statistically significant difference between these two markers in predicting distant metastasis in breast cancer. We hope other researcher interest into exploring more about these markers and their function.


Breast cancer, Distant metastasis, Diagnostic trial, Mitotic activity index, Ki-67

Full Text:



Ghonchech M, Pournamdar Z, Salehiniya H. Incidence and mortality and epidemiology of breast cancer in the World. Asian Pacific J Care Prevention. 2016;17:43-6.

Youlden DR, Cramb SM, Yip CH, Baade PD. Incidence and mortality of female breast cancer in the Asia-Pacific region. Cancer Biol Med. 2014 Jun;11(2):101.

Niryana IW, Dewi NP. Gambaran stadium dan jenis histopatologi kanker payudara di Subbagian Bedah Onkologi RSUP Sanglah Denpasar tahun 2015-2016. Intisari Sains Medis. 2018;9(1):80-4.

Hermansyah D, Albar ZA, Purwanto DJ, Sari L, Putri RI. CD 105 as prognostic factors in advanced stage breast cancer patients. Bali Med J. 2017 Jan 1;6(1):227-35.

Haroon S, Hashmi AA, Khurshid A, Kanpurwala MA, Mujtuba S, Malik B, et al. Ki67 index in breast cancer: correlation with other prognostic markers and potential in pakistani patients. Asian Pac J Cancer Prev. 2013 Jan 1;14(7):4353-8.

Devianti L, Aswiyanti A, and Edison. Peningkatan Ekspresi Ki-67 tidak Berhubungan Dengan Parameter Prognostik Histopatologik Karsinoma Payudara Invasif di Sumatera Barat. Majalah Patologi Indonesia. 2012;21(3):10-6.

Buhmeida A, Al-Maghrabi J, Merdad A, Al-Thubaity F, Chaudhary A, Gari M, Abuzenadah A, et al. Prognostic value of mitotic counts in breast cancer of Saudi Arabian patients. Anticancer Res. 2011 Jan 1;31(1):97-103.

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 1;17(4):323-34.

Baak JP, Van Diest PJ, Janssen EA, Gudlaugsson E, Voorhorst FJ, van der Wall E, et al. Proliferation accurately identifies the high-risk patients among small, low-grade, lymph node-negative invasive breast cancers. Annals Oncol. 2007 Nov 27;19(4):649-54.

Baak JP, van Diest PJ, Voorhorst FJ, van der Wall E, Beex LV, Vermorken JB, et al. Prospective multicenter validation of the independent prognostic value of the mitotic activity index in lymph node-negative breast cancer patients younger than 55 years. J Clin Oncol. 2005;23(25):5993-6001.

Kramer E, Herman O, Frand J, Leibou L, Schreiber L, Vaknine H. Ki67 as a biologic marker of basal cell carcinoma: a retrospective study. IMAJ. 2014 Apr;16(4):229-32.

Kobayashi K, Ito Y, Ogiya A, Gomi N, Horii R, Takahashi S, Hatake K, Akiyama F, Iwase T. Relationship of Ki-67 proliferative index and metastatic tumor of breast cancer. J Clin Oncol. 2013;31(15):1-4.

De Azambuja E, Cardoso F, de Castro Jr G, Colozza M, Mano MS, Durbecq V, et al. Ki-67 as prognostic marker in early breast cancer: a meta-analysis of published studies involving 12 155 patients. Brit J Cancer. 2007 May;96(10):1504.

Narisuari. Gambaran Karakteristik Penderita Kanker Payudara di Poliklinik Bedah Onkologi RSUP Sanglah tahun 2016. Skripsi, Fakultas Kedokteran Universitas Udayana, Denpasar Bali; 2017. Available at:

Partini PD, Niryana IW, Adiputra PA. Karakteristik kanker payudara usia muda di Subbagian Bedah Onkologi Rumah Sakit Umum Pusat Sanglah tahun 2014-2016. Intisari Sains Medis. 2018;9(1):76-9.

Pulido C, Vendrell I, Ferreira AR, Casimiro S, Mansinho A. Alho I, Costa L. Bone metastasis risk factors in breast cancer. E Cancer Medical Sci. 2017;11:715.

Chen MT, Sun HF, Zhao Y, Fu WY, Yang LP, Gao SP, et al. Comparison of patterns and prognosis among distant metastatic breast cancer patients by age groups: a SEER population-based analysis. Scientific Reports. 2017 Aug 23;7(1):9254.

Ribelles N, Santonja A, Pajares B, Llácer C, Alba E. The seed and soil hypothesis revisited: current state of knowledge of inherited genes on prognosis in breast cancer. Cancer Treatment Reviews. 2014 Mar 1;40(2):293-9.

Tjokrowidjaja A, Lee CK, Houssami N, Lord S. Metastatic breast cancer in young women: a population‐based cohort study to describe risk and prognosis. Inter Med J. 2014 Aug;44(8):764-70.

Mitri Z, Constantine T, O'Regan R. The HER2 receptor in breast cancer: pathophysiology, clinical use, and new advances in therapy. Chemotherapy research and practice. 2012 Dec 20;2012.