Correlation of Immunohistochemical Expression of CXCR4 With Clinicopathological Characteristics of Invasive Ductal Carcinoma of Breast
Abstract
Breast cancer is the most frequent malignancy among women worldwide including Iranian women. The different markers have already been investigated for predicting invasion and metastases which one of the most tempting ones is Chemokines. In fact, one of the well-known mediators in the breast cancer metastases is stromal cell-derived factor-1 (SDF-1) CXCR4 chemokine. The CXCR4 chemokine receptor is a G-protein-coupled receptor that selectively binds to SFD-1 (also known as CXCL12). It is obvious that this chemokine receptor plays a critical role in some biologic processes. Nevertheless, there is not enough study to confirm the CXCR4 clinical importance and also its exact prognostic worth in the breast cancer. We carried out this diagnostic study. Immunohistochemically on 70 paraffin blocks of invasive ductal breast carcinoma and adjacent normal tissue simultaneously to assess the expression of CXCR4. The correlation between the presence and intensity of expression of this marker with various clinicopathological factors including age, tumor size, lymph node involvement, stage, and grade are evaluated in all patients. Among the 70 cases, 64 cancer specimens (91.4%) showed CXCR4 expression. It is found out that there is a significant difference between the expression of CXCR4 and the histological grade and lymph node metastasis (P<0.001), but no correlation with other clinicopathologic parameters, such as age, tumor size, and the stage is identified. By considering the CXCR4 intensity, we came across a significant difference between the high expression and the size, stage, histological grade and lymph node metastasis (P<0.001). Breast cancer is the most common invasive tumor to afflict women through the world. According to our study, there is a significant relationship between the expression of CXCR4 and grade, lymph node metastasis in the breast cancer. Furthermore, there is a direct significant correlation between the intensity of expression with grade, stage, tumor size, and lymph node metastasis. Thus, it can be used as a predictor factor for the breast cancer.
Afsharfard A, Mozaffar M, Orang E, Tahmasbpour E. Trends in epidemiology, clinical and histopathological characteristics of breastcancer in Iran: results of a 17yearstudy. Asian Pac J Cancer Prev 2013;14:6905-11.
Ban KA, Godellas CV. Epidemiology of breast cancer. Surg Oncol Clin N Am 2014;23:409-22.
Jazayeri SB, Saadat S, Ramezani R, Kaviani A.Incidence of primary breast cancer in Iran: Ten-year national cancer registry data report. Cancer Epidemiol 2015;39:519-27.
Youlden DR, Cramb SM, Dunn NA, Muller JM, Pyke CM, Baade PD. The descriptive epidemiology of female breast cancer: an international comparison of screening, incidence, survival and mortality. Cancer Epidemiol 2012;36:237-48.
Arveux P, Bertaut A. Epidemiology of breast cancer.Rev Prat 2013;63:1362-6.
Cianfrocca M, Goldstein LJ. Prognostic and predictivefactors in early-stagebreast cancer. Oncologist 2004;9:606-16.
Mukherjee D, Zhao J. The Role of chemokine receptorCXCR4 in breast cancer metastasis. Am J Cancer Res 2013;3:46-57.
Weigelt B, Peterse JL, van't Veer LJ. Breast cancer metastasis: markers and models. Nat Rev Cancer 2005;5:591-602.
Enayatrad M, Amoori N, Salehiniya H. Epidemiology and trends in breast cancer mortality in Iran. Iran J Public Health2015;44:430-1.
Liu Y, Ji R, Li J, Gu Q, Zhao X, Sun T, et al. Correlation effect of EGFR and CXCR4 and CCR7chemokinereceptors in predicting breast cancer metastasis and prognosis. J Exp Clin Cancer Res 2010;29:16.
Müller A, Homey B, Soto H, Ge N, Catron D, Buchanan ME, et al. Involvement of chemokine receptors in breast cancer metastasis. Nature 2001;410:50-6.
Hiller DJ, Meschonat C, Kim R, Li BD, Chu QD. Chemokine receptor CXCR4 level in primary tumors independently predicts outcome for patients with locally advanced breast cancer. Surgery 2011;150:459-65.
Andre F, Xia W, Conforti R, Wei Y, Boulet T, Tomasic G, et al. CXCR4 expression in early breast cancer and risk of distant recurrence. Oncologist 2009;14:1182-8.
Yasuoka H, Tsujimoto M, Yoshidome K, Nakahara M, Kodama R, Sanke T, 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.
Holm NT, Byrnes K, Li BD, Turnage RH, Abreo F, Mathis JM, et al. Elevated levels of chemokine receptor CXCR4 in HER-2 negative breast cancer specimens predict recurrence. J Surg Res 2007;141:53-9.
Andre F, Cabioglu N, Assi H, Sabourin JC, Delaloge S, SahinA, et al. Expression of chemokine receptors predicts the site of meta static relapse in patients with axillary node positive primary breast cancer. Ann Oncol 2006;17:945-51.
Xu TP, Shen H, Liu LX, Shu YQ. The impact of chemokine receptorCXCR4 on breast cancer prognosis: a meta-analysis. Cancer Epidemiol 2013;37:725-31.
Xu C, Zhao H, Chen H, Yao Q. CXCR4 in breast cancer: oncogenic role and therapeutic targeting. Drug Des Devel Ther 2015;9:4953-64.
Sun Y, Mao X, Fan C, Liu C, Guo A, Guan S, et al.CXCL12-CXCR4 axis promotes the natural selection of breast cancer cell metastasis. Tumour Biol 2014;35:7765-73.
Nosrati A, Torabizadeh ZH. Study of Chemokine Marker CXCR4 in Colorectal Cancer in Northern Iran. J Mazandaran Univ Sci 2016:25;60-68.
Taichman RS, Cooper C, Keller ET, Pienta KJ, Taichman NS, McCauley LK. Use of the stromal cell-derived factor-1/CXCR4 pathway in prostate cancer metastasis to bone. Cancer Res 2002;62:1832-7.
Pan J, Mestas J, Burdick MD, Phillips RJ, Thomas GV, Reckamp K, et al. Stromalderivedfactor-1 (SDF-1/CXCL12) and CXCR4 in renal cell carcinoma metastasis. Mol Cancer 2006;5:56.
Spano JP, Andre F, Morat L, Sabatier L, Besse B, Combadiere C, et al. Chemokine receptor CXCR4 and early-stage non-small cell lung cancer: pattern of expression and correlation with outcome. Ann Oncol 2004;15:613-7.
Maréchal R, Demetter P, Nagy N, Berton A, Decaestecker C, Polus M,et al. High expression of CXCR4 may predict poor survival in resected pancreatic adenocarcinoma. Br J Cancer 2009;100:1444-51.
Kang H, Watkins G, Douglas-Jones A, Mansel RE, Jiang WG. The elevated level of CXCR4 is correlated with nodal metastasis of human breast cancer. Breast 2005;14:360-7.
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Issue | Vol 56, No 6 (2018) | |
Section | Original Article(s) | |
Keywords | ||
Breast Invasive ductal carcinoma CXCR4 Clinicopathologic characteristics Immunohistochemistry |
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