Branislav Bystricky1,2, Zuzana Cierna3, Gabriela Sieberova4, Pavol Janega3,5, Marian Karaba4,6, Gabriel Minarik7, Juraj Benca4,6,8, Tatiana Sedlackova7, Silvia Jurisova1,4, Paulina Gronesova9, Daniel Pindak4,6, Jan Macuch4, Jozef Mardiak1,4, Michal Mego10,4,11. 1. 2nd Department of Medical Oncology, Faculty of Medicine, Comenius University, Bratislava, Slovakia. 2. Oncology Department Faculty Hospital Trencin, Trencin, Slovakia. 3. Department of Pathology, Faculty of Medicine, Comenius University, Bratislava, Slovakia. 4. National Cancer Institute, Bratislava, Slovakia. 5. Institute of Normal and Pathological Physiology, Faculty of Medicine, Comenius University, Bratislava, Slovakia. 6. Department of Surgery, Slovak Medical University, Bratislava, Slovakia. 7. Institute of Molecular Biomedicine, Faculty of Medicine, Comenius University, Bratislava, Slovakia. 8. Department of Medicine, St. Elizabeth University, Bratislava, Slovakia. 9. Cancer Research Institute BMC, Slovak Academy of Sciences, Bratislava, Slovakia. 10. 2nd Department of Medical Oncology, Faculty of Medicine, Comenius University, Bratislava, Slovakia misomego@gmail.com. 11. Translational Research Unit, Bratislava, Slovakia.
Abstract
BACKGROUND/AIM: Annexin A2 (ANXA2) is a phospholipid-binding protein involved in fibrinolysis, cell proliferation, migration and metastatic dissemination. Circulating tumor cells (CTCs) are cells responsible for tumor dissemination and have a prognostic value in several types of cancers including breast cancer. Previously, we found correlation between CTCs and activation of coagulation. This study aimed to correlate CTCs with ANXA2 expression on CTCs, tumor cells and tumor associated stroma in primary breast cancer (PBC) patients. PATIENTS AND METHODS: This prospective study included 101 PBC patients treated by primary surgery. CTCs were detected by quantitative real-time polymerase chain reaction (qRT-PCR) assay for the expression of epithelial (CK19) or epithelial-mesenchymal transition (EMT) genes [TWIST1, SNAI1, SNAI2, zinc finger E-box-binding homeobox 1 (ZEB1)]. ANXA2 expression on CTCs was detected by qRT-PCR, while expression of ANXA2 in tumor specimen was evaluated by immunohistochemistry and expressed by a weighted histoscore, evaluating both the percentage of positive cells and the intensity of membrane and cytoplasmic staining. Results of hormone receptors, HER2 status, B-cell lymphoma 2 (bcl-2) protein expression and protein p53 were reported as either positive or negative on histopathology report without further quantification. RESULTS: CTCs were detected in 24.8% patients. Patients with epithelial CTCs had a significantly higher ANXA2 expression on CTCs than those of patients without CTCs (p=0.01). There was no association between CTCs and ANXA2 protein expression in tumor cells. However, patients, whom CTCs with EMT phenotype were detected in, had higher ANXA2 expression in tumor stroma when compared to those with absent EMT CTCs (p=0.04). Hormone-negative tumors had significantly higher ANXA2 expression in tumor cells compared to hormone-positive tumors (p=0.03). Similarly, tumors without bcl-2 protein expression had higher tumor levels of ANXA2 compared to tumor cells that were bcl-2 positive (p=0.05). CONCLUSION: ANXA2 stromal expression might play a key role in aggressive tumor phenotype associated with increased EMT CTCs release, however, other factors beyond ANXA2 are responsible for coagulation activation mediated by CTCs in breast cancer patients. Copyright
BACKGROUND/AIM: Annexin A2 (ANXA2) is a phospholipid-binding protein involved in fibrinolysis, cell proliferation, migration and metastatic dissemination. Circulating tumor cells (CTCs) are cells responsible for tumor dissemination and have a prognostic value in several types of cancers including breast cancer. Previously, we found correlation between CTCs and activation of coagulation. This study aimed to correlate CTCs with ANXA2 expression on CTCs, tumor cells and tumor associated stroma in primary breast cancer (PBC) patients. PATIENTS AND METHODS: This prospective study included 101 PBCpatients treated by primary surgery. CTCs were detected by quantitative real-time polymerase chain reaction (qRT-PCR) assay for the expression of epithelial (CK19) or epithelial-mesenchymal transition (EMT) genes [TWIST1, SNAI1, SNAI2, zinc finger E-box-binding homeobox 1 (ZEB1)]. ANXA2 expression on CTCs was detected by qRT-PCR, while expression of ANXA2 in tumor specimen was evaluated by immunohistochemistry and expressed by a weighted histoscore, evaluating both the percentage of positive cells and the intensity of membrane and cytoplasmic staining. Results of hormone receptors, HER2 status, B-cell lymphoma 2 (bcl-2) protein expression and protein p53 were reported as either positive or negative on histopathology report without further quantification. RESULTS: CTCs were detected in 24.8% patients. Patients with epithelial CTCs had a significantly higher ANXA2 expression on CTCs than those of patients without CTCs (p=0.01). There was no association between CTCs and ANXA2 protein expression in tumor cells. However, patients, whom CTCs with EMT phenotype were detected in, had higher ANXA2 expression in tumor stroma when compared to those with absent EMT CTCs (p=0.04). Hormone-negative tumors had significantly higher ANXA2 expression in tumor cells compared to hormone-positive tumors (p=0.03). Similarly, tumors without bcl-2 protein expression had higher tumor levels of ANXA2 compared to tumor cells that were bcl-2 positive (p=0.05). CONCLUSION:ANXA2 stromal expression might play a key role in aggressive tumor phenotype associated with increased EMT CTCs release, however, other factors beyond ANXA2 are responsible for coagulation activation mediated by CTCs in breast cancerpatients. Copyright
Authors: Michal Mego; Marian Karaba; Tatiana Sedlackova; Juraj Benca; Gabriela Repiska; Lucia Krasnicanova; Jan Macuch; Gabriela Sieberova; Silvia Jurisova; Daniel Pindak; Katarina Kalavska; Jozef Mardiak; Gabriel Minarik Journal: Mol Clin Oncol Date: 2020-04-01
Authors: Noor A Lokman; Carmela Ricciardelli; Andrew N Stephens; Thomas W Jobling; Peter Hoffmann; Martin K Oehler Journal: Diagnostics (Basel) Date: 2021-01-04
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