Immunohistochemical Expression of CD47 in Breast Cancer in Iraqi Female Patients CD47 expression in BC
Abstract
Background: Breast cancer (BC) remains the most prevalent malignancy and a leading cause of cancer-related death among women globally. In Iraq, it is the most commonly diagnosed female cancer. Cluster of Differentiation 47 (CD47), a membrane glycoprotein found on most cells, binds to Signal Regulatory Protein alpha (SIRP alpha) on macrophages to transmit a "don't eat me" signal, inhibiting phagocytosis.
Methods: A total of 100 breast tissue samples were collected from various Iraqi hospitals and laboratories. This retrospective case-control study included 70 malignant and 30 control samples obtained from the Forensic Medicine Institute in Baghdad with official approvals. IHC analysis was done to assess CD47 expression. Chi-square test and Fisher’s exact test were used with Bonferroni correction for multiple comparisons.
Results: CD47 expression showed a statistically significant difference between the malignant tumor group and the non-malignant group. CD47 high expression was observed in malignant cases (61/70, 87.1%) compared to controls (0/30, 0%). No statistically significant association was observed between CD47 expression and pathological stage after Bonferroni correction (p = 0.075).
Conclusion: CD47 expression was associated with malignancy. However, no significant associations between CD47 expression and clinicopathological parameters were confirmed, suggesting that the finding represents an association rather than having a diagnostic or prognostic value. These findings support conducting further research on CD47 to validate these observations and clarify its expression pattern in breast cancer.
References
Kim J, Harper A, McCormack V, Sung H, Houssami N, Morgan E, et al. Global patterns and trends in breast cancer incidence and mortality across 185 countries. Nat Med. 2025;31(4):1154-1162. doi:10.1038/s41591-025-03502-3.
Mustafa IJ, Abdullah OR, Al-Saffar N, Ahmed RF, Fouad M. Quality of life assessment in women with breast cancer in Nineveh, Iraq. Cureus. 2024;16(1):e51589. doi:10.7759/cureus.51589.
Al Zomia AS, Al Zehefa IAM, Lahiq LA, Mirdad MT, Alshahrani AS, Alshahrani T, et al. Tracking the epidemiological trends of female breast cancer in Saudi Arabia since 1990 and forecasting future statistics using Global Burden of Disease data: time-series analysis. BMC Public Health. 2024;24(1):1953. doi:10.1186/s12889-024-19377-x.
Haynes NM, Chadwick TB, Parker BS. The complexity of immune evasion mechanisms throughout the metastatic cascade. Nat Immunol. 2024;25(10):1793-1808. doi:10.1038/s41590-024-01960-4.
Waly AHT, Barraj AH. Estimation of calprotectin, IL-17, and IL-23 levels in the blood of Iraqi patients with Crohn's disease. Egypt J Hosp Med. 2022;88(1):3699-3702. doi:10.21608/ejhm.2022.251212.
Waly AHT, Barraj AH. Prostate cancer in Iraq: a comprehensive literature review of epidemiology, clinical landscape, challenges, and public health strategies. Asian Pac J Cancer Care. 2025;10(3):871-880. doi:10.31557/APJCC.2025.10.3.871-880.
Mohammed SR, Mohamad BJ, Al-Sudani IM. Demographic analysis of breast tumors in a sample of Iraqi population. Opera Med Physiol. 2024;11(1):69-85. doi:10.24412/2500-2295-2024-1-69-85.
Wang C, Feng Y, Patel D, Xie H, Lv Y, Zhao H. The role of CD47 in non-neoplastic diseases. Heliyon. 2023;9(12):e22905. doi:10.1016/j.heliyon.2023.e22905.
Magaki S, Hojat SA, Wei B, So A, Yong WH. An introduction to the performance of immunohistochemistry. Methods Mol Biol. 2019;1897:289-298. doi:10.1007/978-1-4939-8935-5_25.
Ilieva N, Pencheva M, Hadzhiev H, Tashkova D, Daskalova E, Georgiev P, et al. Impact of neoadjuvant therapy on PD-L1 expression in triple-negative breast cancer and correlation with clinicopathological factors. Diagnostics (Basel). 2024;14(23):2672. doi:10.3390/diagnostics14232672.
Liu Y, Wang Y, Yang Y. Emerging phagocytosis checkpoints in cancer immunotherapy. Signal Transduct Target Ther. 2023;8(1):104. doi:10.1038/s41392-023-01365-z.
Sugimura-Nagata A, Koshino A, Inoue S. Expression and prognostic significance of CD47-SIRPA macrophage checkpoint molecules in colorectal cancer. Int J Mol Sci. 2021;22(5):2690. doi:10.3390/ijms22052690.
Melo Garcia L, Barabé F. Harnessing macrophages through the blockage of CD47: implications for acute myeloid leukemia. Cancers (Basel). 2021;13(24):6258. doi:10.3390/cancers13246258.
Chantaraamporn J, Pothipan P, Sakulterdkiat T. CD47 and calreticulin expression in breast cancer subtypes and anti-CD47 inhibitory effects in macrophage-mediated phagocytosis. Anticancer Res. 2024;44(11):4929-4940. doi:10.21873/anticanres.17318.
Celepli P, Karabulut S, Bigat İ, Celepli S, Hücümenoğlu S. CD47 expression and tumor-associated immune cells in breast cancer and their correlation with molecular subtypes and prognostic factors. Pathol Res Pract. 2022;238:154107. doi:10.1016/j.prp.2022.154107.
Park H, Jee S, Bang S. CD47 expression predicts unfavorable prognosis in clear cell renal cell carcinoma after curative resection. Diagnostics (Basel). 2022;12(10):2291. doi:10.3390/diagnostics12102291.
Yuan J, Shi X, Chen C. High expression of CD47 in triple-negative breast cancer is associated with epithelial-mesenchymal transition and poor prognosis. Oncol Lett. 2019;18(3):3249-3255. doi:10.3892/ol.2019.10618.
Park HR, Kim SE, Keam B. Blockade of CD47 enhances the antitumor effect of macrophages in renal cell carcinoma through trogocytosis. Sci Rep. 2022;12(1):12546. doi:10.1038/s41598-022-16766-3.
Yuan J, He H, Chen C. Combined high expression of CD47 and CD68 is a novel prognostic factor for breast cancer patients. Cancer Cell Int. 2019;19:238. doi:10.1186/s12935-019-0957-0.
Kim H, Jee S, Kim Y. Correlation of CD47 expression with adverse clinicopathologic features and an unfavorable prognosis in colorectal adenocarcinoma. Diagnostics (Basel). 2021;11(4):668. doi:10.3390/diagnostics11040668.
Benesova I, Capkova L, Ozaniak A. A comprehensive analysis of CD47 expression in various histological subtypes of soft tissue sarcoma: exploring novel opportunities for macrophage-directed treatments. J Cancer Res Clin Oncol. 2024;150(3):134. doi:10.1007/s00432-024-05661-1.
Luo X, Mo J, Zhang M. CD47: a novel prognostic predictor in epithelial ovarian cancer and correlations with clinicopathological and gene mutation features. World J Surg Oncol. 2024;22(1):44. doi:10.1186/s12957-024-03308-6.
Alhanafy S, Hany H, Nasef K. Immunohistochemical expression of CD47 and CD68 in breast carcinoma and their prognostic value. Asian Pac J Cancer Prev. 2024;25(7):2515-2527. doi:10.31557/APJCP.2024.25.7.2515.
Dawoud MM, Abd El Samie Aiad H, Kasem NS. Is overexpression of CD163 and CD47 in tumour cells of breast carcinoma implicated in the recruitment of tumour-associated macrophages in the tumour microenvironment? An immunohistochemical prognostic study. J Immunoassay Immunochem. 2024;45(4):342-361. doi:10.1080/15321819.2024.2358879.
Chen Y, Klingen TA, Aas H. CD47 and CD68 expression in breast cancer is associated with tumor-infiltrating lymphocytes, blood vessel invasion, detection mode, and prognosis. J Pathol Clin Res. 2023;9(3):151-164. doi:10.1002/cjp2.309.
Xie L, Chen C, Liang X. Expression and clinical significance of various checkpoint molecules in advanced osteosarcoma: possibilities for novel immunotherapy. Orthop Surg. 2023;15(3):829-838. doi:10.1111/os.13620.
Aydin AA, Yuceer RO, Yildirim S. The prognostic significance of CD47, CD68, and CD163 expression levels and their relationship with MLR and MAR in locally advanced and oligometastatic nasopharyngeal carcinoma. Diagnostics (Basel). 2024;14(23):2648. doi:10.3390/diagnostics14232648.
Abd Alkareem FO, Mohamad BJ. Immunohistochemical expression and histopathological role of CD47 in colorectal cancer in Iraqi patients. J Fac Med Baghdad. 2024;66(2):122-128. doi:10.32007/jfacmedbagdad.6622275.
Zhang H, Liu S, Zhang J. CD47 expression in non-small cell lung cancer and its relationship with tumor-associated macrophage infiltration. PLoS One. 2024;19(12):e0314228. doi:10.1371/journal.pone.0314228.
Ye Y, Chen M, Ji F. Survival and clinicopathological significance of CD47 in human solid tumors: an updated systematic review and meta-analysis. Cancer Rep (Hoboken). 2025;8(8):e70296. doi:10.1002/cnr2.70296.
Alhesa A, Awad H, Bloukh S. PD-L1 expression in breast invasive ductal carcinoma with incomplete pathological response to neoadjuvant chemotherapy. Int J Immunopathol Pharmacol. 2022;36:3946320221078433. doi:10.1177/03946320221078433.
Oh HH, Park YL, Park SY, Myung E, Im CM, Yu HJ, et al. CD47 mediates the progression of colorectal cancer by inducing tumor cell apoptosis and angiogenesis. Pathol Res Pract. 2022;240:154220.
Peng Y, Qiu B, Tan F, Xu J, Bie F, He H, et al. TIGIT/CD47 dual high expression predicts prognosis and is associated with immunotherapy response in lung squamous cell carcinoma. Thorac Cancer. 2022;13(14):2014-2023.
Authors
Copyright (c) 2026 Iman Alitemimi
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
Copyright©. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non-Commercial 4.0 International License, which permits copy and redistribution of the material in any medium or format or adapt, remix, transform, and build upon the material for any purpose, except for commercial purposes.