Journal of Pathology and Translational Medicine

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

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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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Distinct profiles of proliferating CD8+/TCF1+ T cells and CD163+/PD-L1+ macrophages predict risk of relapse differently among treatment-naïve breast cancer subtypes
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
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
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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

Clinicopathological Study of 18 Cases of Inflammatory Myofibroblastic Tumors with Reference to ALK-1 Expression: 5-Year Experience in a Tertiary Care Center: Ramesh Babu Telugu, Anne Jennifer Prabhu, Nobin Babu Kalappurayil, John Mathai, Birla Roy Gnanamuthu, Marie Therese Manipadam; J Pathol Transl Med. 2017;51(3):255-263. Published online April 17, 2017; DOI: https://doi.org/10.4132/jptm.2017.01.12

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Abstract PDF

Background
Inflammatory myofibroblastic tumor is a histopathologically distinctive neoplasm of children and young adults. According to World Health Organization (WHO) classification, inflammatory myofibroblastic tumor is an intermediate-grade tumor, with potential for recurrence and rare metastasis. There are no definite histopathologic, molecular, or cytogenetic features to predict malignant transformation, recurrence, or metastasis.
Methods
A 5-year retrospective study of histopathologically diagnosed inflammatory myofibroblastic tumors of various anatomic sites was conducted to correlate anaplastic lymphoma kinase-1 (ALK-1) expression with histological atypia, multicentric origin of tumor, recurrence, and metastasis. Clinical details of all the cases were noted from the clinical work station. Immunohistochemical stains for ALK-1 and other antibodies were performed. Statistical analysis was done using Fisher exact test.
Results
A total of 18 cases of inflammatory myofibroblastic tumors were found during the study period, of which 14 were classical. The female-male ratio was 1:1 and the mean age was 23.8 years. Histologically atypical (four cases) and multifocal tumors (three cases, multicentric in origin) were noted. Recurrence was noted in 30% of ALK-1 positive and 37.5% of ALK-1 negative cases, whereas metastasis to the lung, liver, and pelvic bone was noted in the ALK-1 positive group only.
Conclusions
Overall, ALK-1 protein was expressed in 55.6% of inflammatory myofibroblastic tumors. There was no statistically significant correlation between ALK-1 expression, tumor type, recurrence and metastasis. However, ALK-1 immunohistochemistry is a useful diagnostic aid in the appropriate clinical and histomorphologic context.

Citations

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Case report: Epithelioid inflammatory myofibroblastic sarcoma treated with an ALK TKI ensartinib
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Inflammatory Myofibroblastic Tumour of the Sinonasal Tract with Orbital and Intracranial Extensions Simulating a Malignancy: A Case Report and Review of Literature
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Clinical, pathologic, and molecular features of inflammatory myofibroblastic tumors in children and adolescents
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Pediatric Blood & Cancer.2022;[Epub] CrossRef
Case Report: Early Distant Metastatic Inflammatory Myofibroblastic Tumor Harboring EML4-ALK Fusion Gene: Study of Two Typical Cases and Review of Literature
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A Study of the Correlation between Prognostic Factors of Human Gastric Carcinomas and the Expression of CD44.: Ho Lee, Hyung Chul Kim, Woo Sung Moon, Myoung Jae Kang; Korean J Pathol. 1997;31(9):873-883.

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Abstract PDF: This study was performed to investigate the relationship between CD44 expression and depth of, tumor invasion histopathologic differentiation, tumor size, lymph node metastasis, and proliferating capacity of tumor cells in the gastric carcinoma. In 20 cases of early gastric carcinoma (EGC) and 40 cases of advanced gastric carcinoma (AGC), the immunohistochemical staining for CD44v3, CD44v5, and PCNA gave the following results. 1) In all 60 cases, the positive rates for CD44v3 and CD44v5 were 18.3% and 71.7%, respectively. 2) CD44v5 was expressed in 45% of EGC and 85% of AGC. 3) Larger tumors exhibited higher positive rates for CD44v5. 4) There were 28 cases of lymph node metastases out of 43 cases of CD44v5- positive primary gastric carcinomas (65.1%), and there were 4 cases of lymph node metastases out of 17 CD44v5-negative cases (23.5%). 5) There was no relationship between CD44v5 expression and PCNA index. Because the tumors that exhibit deep invasion, and large in size and have lymph node metastses tend to have more frequent expression of CD44v5, CD44v5 may be one of the useful prognostic markers for gastric carcinoma.

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