Relationship Between Circulating Tumor Cells and Annexin A2 in Early Breast Cancer Patients
| Autor: | Gabriel Minarik, Gabriela Sieberova, Zuzana Cierna, Marian Karaba, Juraj Benca, Paulina Gronesova, Branislav Bystricky, Jozef Mardiak, Pavol Janega, Daniel Pindak, Jan Macuch, Michal Mego, Tatiana Sedlackova, Silvia Jurisova |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Adult Cancer Research Stromal cell Epithelial-Mesenchymal Transition Breast Neoplasms 03 medical and health sciences 0302 clinical medicine Breast cancer Circulating tumor cell Biomarkers Tumor Medicine Humans Annexin A2 Aged Aged 80 and over business.industry General Medicine Middle Aged medicine.disease Neoplastic Cells Circulating Lymphoma SNAI2 030104 developmental biology Oncology Proto-Oncogene Proteins c-bcl-2 030220 oncology & carcinogenesis SNAI1 Cancer research Immunohistochemistry Female business |
| Zdroj: | Anticancer research. 37(5) |
| ISSN: | 1791-7530 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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