KORELASI ANTARA STATUS METASTATIK KELENJAR GETAH BENING AKSILA DENGAN EKSPRESI CD44 DAN CXCR4 PADA KARSINOMA PAYUDARA
DOI:
https://doi.org/10.21776/ub.majalahkesehatan.006.02.7Keywords:
CD44, CXCR4, karsinoma payudara, status metastatik kelenjar getah bening aksilaAbstract
Karsinoma payudara merupakan salah satu keganasan terbanyak yang menyerang wanita di dunia. Salah satu faktor prognosis karsinoma payudara adalah metastasis pada kelenjar getah bening aksila. CD44 merupakan protein transmembran dan penanda sel punca kanker yang memiliki pengaruh pada pertumbuhan tumor, metastasis, dan rekurensi. CXCR4 merupakan reseptor kemokin yang terekspresi pada beberapa sel tumor salah satunya karsinoma payudara. Penelitian ini bertujuan membuktikan adanya korelasi antara status metastatik kelenjar getah bening aksila dengan ekspresi CD44 dan CXCR4 pada karsinoma payudara. Sebanyak 46 sampel blok parafin pasien karsinoma payudara diperoleh dari Instalasi Patologi Anatomik RSUD Dr.Soetomo Surabaya periode Januari- Desember 2017. Blok parafin dipotong dan dilakukan pulasan immunohistokimia dengan antibodi monoklonal CD44 dan CXCR4. Ekspresi CD44 dan CXCR4 dinilai menggunakan skor imunoreaktif (Immunoreactive score (IRS)). Hasil menunjukkan ekspresi CD44 dan CXCR lebih kuat pada karsinoma payudara dengan metastasis kelenjar getah bening aksila dibandingkan tanpa metastasis kelenjar getah bening aksila (p = 0,001 dan p = 0,005). Terdapat korelasi positif yang signifikan antara status metastatik kelenjar getah bening aksila dengan ekspresi CD44 dan CXCR4 (p = 0,001 dan p = 0,004). Kesimpulannya adalah terdapat korelasi yang signifikan antara ekspresi CD44 dan CXCR4 dengan kejadian metastasis kelenjar getah bening pada karsinoma payudara. Hal ini menunjukkan bahwa CD44 dan CXCR4  memiliki peran penting dalam kejadian metastasis kelenjar getah bening pada karsinoma payudara.
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References
Huang M, Li Y, Zhang H, Nan F. Breast Cancer Stromal Fibroblasts Promote the Generation of CD44+CD24- Cells Through SDF-1/CXCR4 Interaction. Journal of Experimental and Clinical Cancer Research. 2010; 29(1): 1–10.
Kishima MO, de Oliveira CEC, Banin-Hirata BK, Losi-Guembarovski R, de Oliveira KB, Amarante MK, et al. Immunohistochemical Expression of CXCR4 on Breast Cancer and its Clinical Significance. Analytical Cellular Pathology. 2015; 2015: 1-6.
Pusat Data dan Informasi Kesehatan RI. Infodatin. Kementerian Kesehatan RI. (Online). 2015. http://www.depkes.go.id/resources/download/pusdatin/infodatin/infodatin-kanker.pdf. Diunduh tanggal 7 April 2018.
Colditz G, Chia KS. Invasive vreast carcinoma: Introduction and general features. In: Lakhani SR, Ellis IO, Schnitt SJ, Tan PH, de Vijver MJ (Ed). WHO Classification of Tumours of the Breast. 4th edition. Lyon: International Agency for Research on Cancer (IARC). 2012. p.14-21.
Mukherjee D, Zhao J. The Role of Chemokine Receptor CXCR4 in Breast Cancer Metastasis. American journal of cancer research. 2013; 3(1): 46–57.
Sun Y, Mao X, Fan C, Liu C, Guo A, et al. CXCL12-CXCR4 axis promotes the natural selection of breast cancer cell metastasis. Tumor Biology. 2014; 35(8): 7765–7773.
Louderbough JMV, Schroeder JA. Understanding the Dual Nature of CD44 in Breast Cancer Progression. Molecular Cancer Research. 2011;9(12): 1573-1586.
Basakran NS. CD44 as a Potential Diagnostic Tumor Marker. Saudi Medical Journal. 2015; 36(3): 273–279.
Li W, Ma H, Zhang J, Zhu L, Whang C,et al. Unraveling the Roles of CD44/CD24 and ALDH1 as Cancer Stem Cell Markers in Tumorigenesis and Metastasis. Scientific Reports. 2017; 7(1): 1–15.
Fuchs K, Hippe A, Schmaus A, Homey B., Sleeman JP, et al. Opposing Effects of High-and Low-molecular Weight Hyaluronan on CXCL12-induced CXCR4 Signaling Depend on CD44. Cell Death and Disease. 2013 ;4(10): 1-11.
Orian-Rousseau V. CD44 Acts as a Signaling Platform Controlling Tumor Progression and Metastasis. Frontiers in Immunology. 2015; 6(APR): 10–13.
Ma L, Jiang T. Clinical implications of Ezrin and CD44 co-expression on breast cancer. Oncology Reports. 2013; 30: 1899-1905.
Sheridan C, Kishimoto H, Fuchs RK, Mehrotra S, Bhat-Nakshatri P, et al. CD44+/CD24- breast cancer cells exhibit enhanced invase properties: An early step necessary for metastasis. Breast Cancer Research. 2006; 8(5): 1–13.
Sun DY, Yu H, Qiu XB, Li G, Zhang N. Relationships between CD44, hyaluronic acid expression and lymphatic metastasis and radiosensitivity of nasopharyngeal carcinoma. Biomedical Research. 2016; 27(2): 286-291.
Thapa R, Wilson GD. The Importance of CD44 as a Stem Cell Biomarker and Therapeutic Target in Cancer. Stem Cells International. 2016; 2016: 1-15.
Chanmee T, Ontong P, Kimata K, Itano N. Key Roles of Hyaluronan and Its CD44 Receptor in the Stemness and Survival of Cancer Stem Cells. Frontiers in Oncology. 2015; 5(180): 1–11.
Vira D, Basak SK, Veena MS, Wang MB, Batra RK, et al. Cancer Stem Cells, microRNAs, and Therapeutic Strategies Including Natural Products. Cancer and Metastasis Reviews. 2012; 31(3–4): 733–751.
Xu C, Zhao H, Chen H, Yao Q. CXCR4 in Breast Cancer: Oncogenic Role And Therapeutic Targeting. Drug Design, Development and Therapy. 2015; 9: 4953–4964.
Dayer R, Babashah S, Jamshidi S, Sadeghizadeh M. Upregulation of CXC Chemokine Receptor 4-CXC Chemokine Ligand 12 Axis in Invasive Breast Carcinoma: A Potent Biomarker Predicting Lymph Node Metastasis. J Can Res Ther. 2018;14: 345-350.
Cabioglu N, Yazici MS, Arun B, Broglio KR, Hortobagyi GN, et al. CCR7 and CXCR4 as Novel Biomarkers Predicting Axillary Lymph Node Metastasis in T1 Breast Cancer. Clin Cancer Res. 2005; 11(16): 5686-5693.
Hiller D, Chu QD. CXCR4 and Axillary Lymph Nodes: Review of Potential Biomarker for Breast Cancer Metastasis. International Journal of Breast Cancer. 2011; 2011: 1-6.
Fischer T, Nagel F, Jacobs S, Stumm R, Schulz S. Reassesment of CXCR4 Chemokine Receptor Expression in Human Normal and Neoplastic Tissue Using Novel Rabbit Monoclonal Antibody UMB-2. PloS ONE. 2008; 3(12): 1-7.
Domanska UM, Kruizinga RC, Nagengast WB, Timmer-Bosscha H, Huls G, et al. A Review on CXCR4/CXCL12 Axis in Oncology: No Place to Hide. European Journal of Cancer. 2013; 49(1): 219–230.
Cojoc, M., Peitzsch, C., Trautmann, F., Polishchuk, L., Telegeev, G.D., Dubrovska, A. Emerging Targets in Cancer Management: Role of the CXCL12/CXCR4 Axis. Onco Targets and Therapy. 2013;6: 1347-1361.
Yasuoka H, Tsujimoto M, Yoshidome K, Nakahara M, Kodama R, et al. Cytoplasmic CXCR4 Expression in Breast Cancer: Induction by Nitric Oxide and Correlation with Lymph Node Metastasis and Poor Prognosis. BMC Cancer. 2008; 8(340):1-10.
Salvucci O, Bouchard A, Baccarelli A, Deschenes J, Sauter G, et al. The Role of CXCR4 Receptor Expression in Breast Cancer: A Large Tissue Microarray Study. Breast Cancer Research and Treatment. 2006; 97(3): 275–283.
Speetjens FM, Liefers GJ, Korbee CJ, Mesker WE, van de Velde CJH, et al. Nuclear Localization of CXCR4 Determines Prognosis for Colorectal Cancer Patients. Cancer Microenvironment. 2009; 2: 1-7.
Wang L, Wang Z, Yang B, Yang Q., Wang L, et al. CXCR4 Nuclear Localization Follows Bindings of its Ligand SDF-1 and Occurs in Metastatic but Not Primary Renal Cell Carcinoma. Oncology Reports. 2009; 22: 1333-1339.
Ma Q, Zhou Y, Ma B, Chen X, Wen Y, et al. The Clinical Value of CXCR4, HER2 and CD44 in Human Osteosarcoma: A Pilot Study. Oncology Letters. 2012; 3(4): 797–801.
Bao W, Fu H-J, Xie Q-S, Wang L, Zhang R, et al. HER2 Interacts with CD44 to Up-regulate CXCR4 via Epigenetic Silencing of microRNA-139 in Gastric Cancer Cells. Gastroenterology. 2011; 141: 2076-2087.
