Comparison Between Serum S100A8/A9 and CA 15-3 in the Diagnosis of Breast Carcinoma

Rifat Mahbuba Rob¹, Amit Kumar Pramanik^2, , Sheuly Ferdoushi³, Chitra Das⁴, Debatosh Paul³, Joysree Das Joya⁵, Md. Saiful Islam³ and Mst. Shaila Yesmin³

¹Laboratory Service Division, National Institute of Burn and Plastic Surgery, Dhaka, Bangladesh

²Upazila Health Complex, Shibganj, Chapainawabganj, Bangladesh

³Department of Laboratory Medicine, Bangabandhu Sheikh Mujib Medical University (BSMMU), Shahbag, Dhaka, Bangladesh

⁴Directorate General of Health Services (DGHS), Dhaka, Bangladesh

⁵Department of Laboratory Medicine, National Institute of Traumatology and Orthopedic Rehabilitation, Dhaka, Bangladesh

Cite this paper:
Rifat Mahbuba Rob, Amit Kumar Pramanik, Sheuly Ferdoushi, Chitra Das, Debatosh Paul, Joysree Das Joya, Md. Saiful Islam and Mst. Shaila Yesmin. Comparison Between Serum S100A8/A9 and CA 15-3 in the Diagnosis of Breast Carcinoma. International Journal of Clinical and Diagnostic Research. 2025; 12(1):1-4. doi: 10.12691/ijcdr-12-1-1

Abstract

Carcinoma of the breast is the most common public health concern in women globally. Early diagnosis of breast carcinoma reduces the disease burden. Serum S100A8/A9, a calcium-binding protein involved in tumorigenesis, may be a useful biomarker for breast cancer diagnosis, and this study investigated its comparison with CA15-3. This cross-sectional comparative study, conducted from March 2021 to February 2022, involved 74 clinically suspected cases of breast carcinoma at Department of Laboratory Medicine in Bangabandhu Sheikh Mujib Medical University Dhaka, Bangladesh. Patients were categorized into Group I (breast carcinoma) and Group II (benign breast tumor) based on histopathology reports. After informed consent, 5.0 ml of venous blood was collected for serum S100A8/A9 and CA 15-3 estimation, which were then serologically assessed using ELISA and chemiluminescence methods. This study found that breast carcinoma patients had statistically significant (P ≤ 0.001) higher mean levels of S100A8/A9 (7.14 ± 3.11 μg/mL) and CA 15-3 (50.73 ± 112.9 U/mL) compared to S100A8/A9 (4.14 ± 1.93 μg/mL) and for CA 15-3 (10.76 ± 3.43 U/mL) for benign breast tumour. The receiver operating characteristic (ROC) analysis indicated that the optimal cut-off value for serum S100A8/A9 was 4.61, with a sensitivity of 78.4% and specificity of 70.3%, yielding an area under the curve (AUC) of 0.789. Similarly, the cut-off value for CA 15-3 was 11.85, with a sensitivity of 70.3% and specificity of 64.9%, and an AUC of 0.743. With significant levels of sensitivity and specificity, serum S100A8/A9 levels emerge as a valuable diagnostic tool for identifying breast carcinoma.

Keywords:
Breast Carcinoma Serum S100A8/A9 Serum CA 15-3 Benign Breast Tumour

This work is licensed under a Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

References:

[1]	Akram M, Iqbal M, Daniyal M, Khan AU. Awareness and current knowledge of breast cancer. Biological research. 2017 Dec; 50(1): 1-23.
[2]	Momenimovahed Z, Salehiniya H. Epidemiological characteristics of and risk factors for breast cancer in the world. Breast Cancer: Targets and Therapy. 2019; 11: 151.
[3]	World Health Organization (WHO), 2021. Breast cancer. Available from https:// www.who.int/ news-room/fact-sheets/detail/breast-cancer. [Accessed May. 2, 2021].
[4]	World Health Organization (WHO), 2021. International Agency for research on cancer, Globocan, 2020. Available from https://gco.iarc.fr/. [Accessed May. 2, 2021].
[5]	Diamandis EP, editor. Tumor markers: physiology, pathobiology, technology, and clinical applications. Amer. Assoc. for Clinical Chemistry; 2002.
[6]	Donepudi MS, Kondapalli K, Amos SJ, Venkanteshan P. Breast cancer statistics and markers. Journal of cancer research and therapeutics. 2014 Jul 1; 10(3): 506.
[7]	Duffy MJ, Shering S, Sherry F, McDermott E, O'higgins N. CA 15–3: a prognostic marker in breast cancer. The International journal of biological markers. 2000 Oct; 15(4): 330-3.
[8]	Duffy MJ, Evoy D, McDermott EW. CA 15-3: uses and limitation as a biomarker for breast cancer. Clinica chimica acta. 2010 Dec 14; 411(23-24): 1869-74.
[9]	Hattrup CL, Gendler SJ. Structure and function of the cell surface (tethered) mucins. Annu. Rev. Physiol.. 2008 Mar 17; 70: 431-57.
[10]	Kufe DW. Mucins in cancer: function, prognosis and therapy. Nature Reviews Cancer. 2009 Dec; 9(12): 874-85.
[11]	Shering SG, Sherry F, McDermott EW, O'Higgins NJ, Duffy MJ. Preoperative CA 15‐3 concentrations predict outcome of patients with breast carcinoma. Cancer: Interdisciplinary International Journal of the American Cancer Society. 1998 Dec 15; 83(12): 2521-7.
[12]	Wild D, editor. The immunoassay handbook: theory and applications of ligand binding, ELISA and related techniques. Newnes; 2013 Jan 21.
[13]	Kamil AN, Saleh BO, Alani KH. Dyslipidemia and CA15-3 serum level in Iraqi Women with Breast Tumor: A Comparative Study. Journal of the Faculty of Medicine Baghdad. 2018 Dec 31; 60(3): 160-5.
[14]	Khorrami S, Tavakoli M, Safari E. Clinical value of serum S100A8/A9 and CA15-3 in the diagnosis of breast cancer. Iranian journal of pathology. 2019; 14(2): 104.
[15]	Nakatani Y, Yamazaki M, Chazin WJ, Yui S. Regulation of S100A8/A9 (calprotectin) binding to tumor cells by zinc ion and its implication for apoptosis-inducing activity. Mediators of inflammation. 2005 Oct 24; 2005(5): 280-92.
[16]	Lim SY, Yuzhalin AE, Gordon-Weeks AN, Muschel RJ. Tumor-infiltratingmonocytes/macrophages promote tumor invasion and migration by upregulating S100A8 and S100A9 expression in cancer cells. Oncogene. 2016 Nov; 35(44): 5735-45.
[17]	Drews-Elger K, Iorns E, Dias A, Miller P, Ward TM, Dean S, Clarke J, Campion-Flora A, Rodrigues DN, Reis-Filho JS, Rae JM. Infiltrating S100A8+ myeloid cells promote metastatic spread of human breast cancer and predict poor clinical outcome. Breast cancer research and treatment. 2014 Nov; 148(1): 41-59.
[18]	Goh JY, Feng M, Wang W, Oguz G, Yatim SM, Lee PL, Bao Y, Lim TH, Wang P, Tam WL, Kodahl AR. Chromosome 1q21. 3 amplification is a trackable biomarker and actionable target for breast cancer recurrence. Nature medicine. 2017 Nov; 23(11): 1319-30.
[19]	Khammanivong A, Sorenson BS, Ross KF, Dickerson EB, Hasina R, Lingen MW, Herzberg MC. Involvement of calprotectin (S100A8/A9) in molecular pathways associated with HNSCC. Oncotarget. 2016 Mar 22; 7(12): 14029.
[20]	Kandylis K, Vassilomanolakis M, Baziotis N, Papadimitriou A, Tsoussis S, Ferderigou A, Efremidis AP. Diagnostic significance of the tumour markers CEA, CA 15–3 and CA 125 in malignant effusions in breast cancer. Annals of Oncology. 1990 Nov 1; 1(6): 435-8.
[21]	Hashim ZM. The significance of CA15-3 in breast cancer patients and its relationship to HER-2 receptor status. International Journal of Immunopathology and Pharmacology. 2014 Jan; 27(1): 45-51.
[22]	Giovanella L, Ceriani L, Giardina G, Bardelli D, Tanzi F, Garancini S. Serum cytokeratin fragment 21.1 (CYFRA 21.1) as tumour marker for breast cancer: comparison with carbohydrate antigen 15.3 (CA 15.3) and carcinoembryonic antigen (CEA).
[23]	MT AF, Darko E, Addai BW. The use of carbohydrate antigen (CA) 15-3 as a tumor marker in detecting breast cancer. Pakistan Journal of Biological Sciences: PJBS. 2008 Aug 1; 11(15): 1945-8.
[24]	Uygur MM, Gümüş M. The utility of serum tumor markers CEA and CA 15–3 for breast cancer prognosis and their association with clinicopathological parameters. Cancer Treatment and Research Communications. 2021 Jan 1; 28: 100402.