ORIGINAL ARTICLE Bali Medical Journal (Bali MedJ) 2021, Volume 10, Number 1: 99-102 P-ISSN.2089-1180, E-ISSN: 2302-2914 Correlation of CD44 and CD24 expression with the positive response after neoadjuvant Published by Bali Medical Journal chemotherapy in stage IIIB breast cancer patient at Dr. Saiful Anwar Hospital, Malang, Indonesia Muhammad Bachtiar Budianto1*, Artono Isharanto2, Andry Haris3 1Department of Oncology Surgery, ABSTRACT Faculty of Medicine, Universitas Brawijaya, Malang, Indonesia Background: Breast cancer is a type of cancer due to abnormal cell growth of breast tissue. CD44 and CD24 is a potential 2 Department of Thoracic and target in breast cancer therapy. This study aims to evaluate the responsiveness of stage 3 breast cancer to chemotherapy by Cardiovascular Surgery, Faculty of measuring the expression levels of CD44 and CD24 molecules. Medicine, Universitas Brawijaya, Malang, Indonesia Methods: We conducted an observational study with pre-and –post-intervention or test research types. This study was 3General Surgery Resident, Faculty of performed on 49 Luminal Stadium IIIB subtype breast cancer patients who received 3 series of neoadjuvant chemotherapy at Medicine, Universitas Brawijaya, Malang, RSUD dr. Saiful Anwar Malang, immunohistochemical examination, and painting of tissue specimens from the biopsy results. Indonesia Data were analyzed using SPSS version 20 for Windows. Results: Based on the Paired t-test and discriminant analysis, there were no significant differences between CD44 and CD24 expression before and after chemotherapy (p=0.501 and p=0.097, respectively). Therefore, the results of the study prompt *Corresponding author: that the expression of CD44 and CD24 could not be a predictor of the chemotherapy response. Muhammad Bachtiar Budianto; Conclusion: There are different expressions of CD44 and CD44 in primary breast cancer before and after chemotherapy, but Department of Oncology Surgery, Faculty no significant difference was found. of Medicine, Universitas Brawijaya, Malang, Indonesia; [email protected] Keywords: CD44, CD24, Expression, Breast Cancer. Cite This Article: Budianto, M.B., Isharanto, A., Haris, A. 2021. Correlation of CD44 and CD24 expression with the positive Received: 2020-12-08 response after neoadjuvant chemotherapy in stage IIIB breast cancer patient at Dr. Saiful Anwar Hospital, Malang, Indonesia. Accepted: 2021-03-16 Bali Medical Journal 10(1): 99-102. DOI: 10.15562/bmj.v10i1.2123 Published: 2021-04-01 INTRODUCTION CD44 is a multifunctional CD24 is said to be a potential target transmembrane Class 1 glycoprotein therapy for osteosarcoma, gastric cancer, Breast cancer is a type of cancer due to found in normal cells and highly and breast cancer. So, the expression abnormal cell growth of breast tissue. The expressed in cancer cells.4 CD44 marks levels of CD24 can be used as a marker breast tissue comprises the mammary cell migration, proliferation, growth, to estimate the sensitivity of these cancer gland, adipose tissue, lactiferous duct, and progressivity, and the tumor on the cell cells.7 sinus & lymph nodes. Abnormal cells can membrane.4 CD44 expression initiates Based on those mentioned above, grow in any part of the breast and cause 1 the development of the tumor by binding the purpose of this study is to evaluate slow but inevitable destruction. The with receptors such as tyrosine kinase.4,5 the responsiveness of stage 3 breast incidence of breast cancer has increased This cell marker has been used to evaluate cancer to chemotherapy by measuring consistently and has risen by 50% between 2 the effectiveness of drugs targeting the expression levels of CD44 and CD24 1965 and 1985. In Indonesia, based progenitor cells.5 CD44 is also a type of molecules. Since stage 3 breast cancer on the national database Basic Health adhesive molecule. Meanwhile, CD24 is is inoperable, it requires neoadjuvant Research data, breast cancer was the most a glycosyl-phosphatidyl-inositol protein chemotherapy to reduce the size or lymph common cancer in women in 2013, with a molecule responsible for the proliferation node metastasis (tumor-free margin). As prevalence of 17 – 25 cases out of 100.000 3 of tumor cells and an increase of this another reason, this study is conducted on population. It was the most admitted protein can cause metastasis.5 Hence, this breast cancer with lymph node metastasis cancer cases compared to other cancers protein is linked to cancer cell metastasis where CD44 and CD42 easily can be (28.7%). Based on the same database, the and chemotherapeutic resistance. differentiated so the correlation between prevalence of breast cancer reached 0.5 in 3 CD24 expression is correlated with chemotherapy and both CD44 and CD24 1000 Indonesian women. carcinogenesis and tumor progression.6 levels can be measured. PublishedOpen access: by Baliwww.balimedicaljournal.org Medical Journal | Bali Medical Journal 2021; 10(1): 99-102 | doi: 10.15562/bmj.v10i1.2123 99 ORIGINAL ARTICLE METHODS Table 1. Classification of breast cancer based on molecular subtype This is an observational study with pre Subtype Prevalence (%) Tendency Prognosis and post test observation. The population Basal-like 15.0-20.0 ER/PR/HER2 negatif Shortest Survival of this study was all stage IIIB breast HER-2+ 10.0-15.0 ER(-), PR(-), HER(+) Shortest Survival cancer patients treated at RSUD dr. Saiful Luminal A 40.0 ER and/or PR(+), HER2(-) Longest Survival Anwar Malang from December 2019 to low, and Ki67 April 2020. The data collection process was conducted using total sampling with Table 2. Average number of CD44 and CD23 expression before and after all patients who were diagnosed with chemotherapy stage IIIB breast cancer subtype luminal Mean (A and B) based on pathology anatomy Variables Minimum Maximum Mean±SD P Difference examination and immunohistochemistry, who were maximum 65 years old with CD24 Karnofsky scale >70%, and agreed Before 3.00 20.00 11.53±3.94 1.592 0.097 After 3.00 19.00 9.93±4.56 with consent to undergo biopsy and CD44 neoadjuvant chemotherapy combination Before 3.00 20.00 11.87±4.06 0.306 0.501 for 3 series. Patient with the presence of After 2.00 19.00 11.57±4.05 distant metastasis based on a physical and radiologic examination, comorbid that contraindicate to do chemotherapy RESULTS in CD44 expression before chemotherapy. From the data on the average expression such as congestive heart failure, history of According to the breast cancer of CD44 and CD 24, it was seen that there acute myocardial infarction, chronic liver classification, most of the respondents was a decrease in the mean expression of disease, chronic kidney disease; patient were in the Luminal A subtype (40.0%), CD44 and CD 24 before chemotherapy with a history of previous tumor resection which had the most prolonged survival was performed compared with after and undergo other chemotherapy and based on the prognosis, followed by the chemotherapy (Figure 1). administration of hormonal therapy were Basal-like subtype (15.0-20.0%), and Based on the results in Table 2, it was all excluded in this study. Gender, age, HER-2+ subtype (10.0-15.0%) (Table 1). cause, operation, duration of treatment, found that the mean between CD44 and The following data were from CD44 CD24 expressions before chemotherapy condition of the patient on discharge were and CD24 expression in 49 patients with the variables studied. with CD44 and CD 24 expressions after locally advanced stage IIIB breast cancer chemotherapy was given was 0.306 and This study data were the result of Luminal subtype (Table 2). Minimum biomolecular measurements in the form 1.592, which showed a tendency to change CD44 expression was 2 and maximum the expression of CD44 and CD24 with an of expression of CD44 and CD 24 in CD44 expression was 19 in patients patients with locally advanced stage IIIB average of 0.306 and 1.592. with locally advanced breast cancer IIIB Evaluation of CD44 and CD24 breast cancer Luminal subtype where Luminal subtype before chemotherapy. breast cancer tissue is taken from the was assessed by pathologists blindly, The minimum and maximum CD24 randomly, and without knowledge of the biopsy results. The study sample was expression were 3 and 20 in patients divided into 2 large groups namely groups study and was examined with a 100 times with locally advanced breast cancer IIIB magnification light microscope in 10 visual with CD24 and CD44 expressions. The Luminal subtype after chemotherapy, CD24 expression group is further divided fields to assess the intensity and quantity respectively (Table 2). of immunostaining. Immunostaining is into 2 small groups namely the group The mean cut-off values, from the with CD24 expression before neoadjuvant grouped based on the following staining highest values of CD44 and CD24 before reactions: (1) shows the intensity of chemotherapy and CD24 expression after chemotherapy and after chemotherapy, neoadjuvant chemotherapy. The CD44 weak cytoplasmic staining, (2) shows were compared with the lowest values to the intensity of moderate cytoplasmic expression group is also further divided evaluate whether there were significant into 2 small groups namely the group staining, (3) shows the intensity of strong differences between before and after cytoplasmic staining, and (4) shows with CD44 expression before neoadjuvant chemotherapy. The average data of CD44 chemotherapy and CD44 expression after the intensity of very strong cytoplasmic and CD24 expressions found that the staining. (Figure 2A-2D). Data obtained neoadjuvant chemotherapy. mean expression of CD44 and CD24 The data were analyzed with the were qualitatively assessed and calculated before chemotherapy was higher than the by the reaction of strong intensity and SPSS version 20 for Windows using a mean expression of CD44 and CD24 after Paired t-test and multivariate test for the very strong only because of the reagent’s chemotherapy, with the lowest CD44 and reactivity that shows the nature of the expression of CD44 and CD24 before and CD24 expression on CD24 expression after after neoadjuvant chemotherapy.