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Original Articles
- High Cytoplasmic CXCR4 Expression Predicts Prolonged Survival in Triple-Negative Breast Cancer Patients Treated with Adjuvant Chemotherapy
- Bobae Shim, Min‐Sun Jin, Ji Hye Moon, In Ae Park, Han Suk Ryu
- J Pathol Transl Med. 2018;52(6):369-377. Published online October 1, 2018
- DOI: https://doi.org/10.4132/jptm.2018.09.19
- 12,179 View
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- 9 Web of Science
- 11 Crossref
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Abstract
PDF - Background
Chemokine receptor CXC chemokine receptor type 4 (CXCR4) and its ligand CXC motif chemokine 12 (CXCL12; stromal cell-derived factor-1) are implicated in tumor growth, metastasis, and tumor cell-microenvironment interaction. A number of studies have reported that increased CXCR4 expression is associated with worse prognosis in triple-negative breast cancer (TNBC), but its prognostic significance has not been studied in TNBC patients treated with adjuvant chemotherapy.
Methods
Two hundred eighty-three TNBC patients who received adjuvant chemotherapy were retrospectively analyzed. Tissue microarray was constructed from formalinfixed, paraffin-embedded tumor tissue and immunohistochemistry for CXCR4 and CXCL12 was performed. Expression of each marker was compared with clinicopathologic characteristics and outcome.
Results
High cytoplasmic CXCR4 expression was associated with younger age (p = .008), higher histologic grade (p = .007) and lower pathologic stage (p = .045), while high CXCL12 expression was related to larger tumor size (p = .045), positive lymph node metastasis (p = .005), and higher pathologic stage (p = .017). The patients with high cytoplasmic CXCR4 experienced lower distant recurrence (p = .006) and better recurrence-free survival (RFS) (log-rank p = .020) after adjuvant chemotherapy. Cytoplasmic CXCR4 expression remained an independent factor of distant recurrence (p = .019) and RFS (p = .038) after multivariate analysis.
Conclusions
High cytoplasmic CXCR4 expression was associated with lower distant recurrence and better RFS in TNBC patients treated with adjuvant chemotherapy. This is the first study to correlate high CXCR4 expression to better TNBC prognosis, and the underlying mechanism needs to be elucidated in further studies. -
Citations
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Konstantinos Ntostoglou, Sofia D. P. Theodorou, Tanja Proctor, Ilias P. Nikas, Sinclair Awounvo, Athanasia Sepsa, Vassilis Georgoulias, Han Suk Ryu, Ioannis S. Pateras, Christos Kittas
Cancer Immunology, Immunotherapy.2024;[Epub] CrossRef - Unravelling the CXCL12/CXCR4 Axis in breast cancer: Insights into metastasis, microenvironment interactions, and therapeutic opportunities
Priyanka Garg, Venkateswara Rao Jallepalli, Sonali Verma
Human Gene.2024; 40: 201272. CrossRef - New Emerging Chemokine Receptors: CCR5 or CXCR5 on Tumor Is Associated with Poor Response to Chemotherapy and Poor Prognosis in Locally Advanced Triple-Negative Breast Cancer
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Cells.2024; 13(16): 1334. CrossRef - Associations of CXCL12 polymorphisms with clinicopathological features in breast cancer: a case-control study
Shuai Lin, Yi Zheng, Meng Wang, Linghui Zhou, Yuyao Zhu, Yujiao Deng, Ying Wu, Dai Zhang, Na Li, Huafeng Kang, Zhijun Dai
Molecular Biology Reports.2022; 49(3): 2255. CrossRef - The clinicopathological and prognostic value of CXCR4 expression in patients with lung cancer: a meta-analysis
Liping Qiu, Yuanyuan Xu, Hui Xu, Biyun Yu
BMC Cancer.2022;[Epub] CrossRef - Demystifying the CXCR4 conundrum in cancer biology: Beyond the surface signaling paradigm
Mushtaq Ahmad Nengroo, Muqtada Ali Khan, Ayushi Verma, Dipak Datta
Biochimica et Biophysica Acta (BBA) - Reviews on Cancer.2022; 1877(5): 188790. CrossRef - Targeted dendrimers for antagonizing the migration and viability of NALM-6 lymphoblastic leukemia cells
Chuda Chittasupho, Chaiyawat Aonsri, Witcha Imaram
Bioorganic Chemistry.2021; 107: 104601. CrossRef - CXCR4 and RANK Combination as a Predictor of Breast Cancer Bone Metastasis in Indonesia
Yulian Erwin D
Journal of Surgery and Surgical Research.2021; : 020. CrossRef - CXCL12/CXCR4 axis in the microenvironment of solid tumors: A critical mediator of metastasis
Keywan Mortezaee
Life Sciences.2020; 249: 117534. CrossRef - Impact of the Chemokine Receptors CXCR4 and CXCR7 on Clinical Outcome in Adrenocortical Carcinoma
Irina Chifu, Britta Heinze, Carmina T. Fuss, Katharina Lang, Matthias Kroiss, Stefan Kircher, Cristina L. Ronchi, Barbara Altieri, Andreas Schirbel, Martin Fassnacht, Stefanie Hahner
Frontiers in Endocrinology.2020;[Epub] CrossRef
- Distinct profiles of proliferating CD8+/TCF1+ T cells and CD163+/PD-L1+ macrophages predict risk of relapse differently among treatment-naïve breast cancer subtypes
- Association of CXCR4 Expression with Metastasis and Survival among Patients with Non-small Cell Lung Cancer.
- Joon Seon Song, Jin Kyung Jung, Jong Chul Park, Dong Kwan Kim, Se Jin Jang
- Korean J Pathol. 2008;42(6):358-364.
- 1,808 View
- 25 Download
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Abstract
PDF
- BACKGROUND
Expression of CXCR4 chemokine receptor, initially described to be involved in the homing of lymphocytes in inflammatory tissue, on breast cancer cell lines is associated with the development of lung metastases. In the present study, we evaluated CXCR4 expression in patients with non-small cell lung cancer (NSCLC). METHODS: Tissue microarray blocks were constructed from 408 formalin-fixed, paraffin-embedded NSCLC samples and analyzed via immunohistochemical staining. RESULTS: We observed CXCR4 expression in 214 (66.3%) of the 323 tumors with cytoplasmic or nuclear staining patterns. These tumors were then divided into 109 negative, 166 weak-positive and 48 strong-positive expression groups. Strong expression of CXCR4 correlated with NSCLC recurrence (p=0.047) and distant metastasis (p=0.035). However, lymph node metastasis (p=0.683) and locoregional recurrence (p=0.856) were not associated with CXCR4 expression. Interestingly, the median overall survival times relative to CXCR4 expression were 71 months in the CXCR4-negative group, 43 months in the weakly positive CXCR4 group and 23 months in the strongly positive CXCR4 group. Strongly positive CXCR4 staining was associated with significantly worse outcomes (p=0.005, log-rank test).
CONCLUSIONS
Expression of CXCR4 was associated with distant NSCLC metastases and shorter survival times.
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