Relationship Between Circulating Tumor Cells and Annexin A2 in Early Breast Cancer Patients
Relationship Between Circulating Tumor Cells and Annexin A2 in Early Breast Cancer Patients
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DOI：
10.21873/anticanres.11624
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发表时间：
2017-05-01
影响因子：
2
通讯作者：
Mego, Michal
中科院分区：
文献类型：
--
作者：
Bystricky, Branislav;Cierna, Zuzana;Mego, Michal
背景/目的：膜联蛋白A2（ANXA 2）是一种磷脂结合蛋白，参与纤维蛋白溶解、细胞增殖、迁移和转移性播散。循环肿瘤细胞（CTC）是负责肿瘤扩散的细胞，在包括乳腺癌在内的几种类型的癌症中具有预后价值。以前，我们发现CTC和凝血激活之间的相关性。本研究旨在将原发性乳腺癌（PBC）患者中CTC与CTC、肿瘤细胞和肿瘤相关基质上的ANXA 2表达相关联。患者和方法：这项前瞻性研究包括101例原发性手术治疗的PBC患者。通过定量实时聚合酶链反应（qRT-PCR）检测CTC的上皮（CK 19）或上皮-间充质转化（EMT）基因[TWIST 1、SNAI 1、SNAI 2、锌指E-box结合同源框1（ZEB 1）]的表达。通过qRT-PCR检测CTC上的ANXA 2表达，而通过免疫组织化学评估肿瘤标本中的ANXA 2表达，并通过加权组织评分来表达，评估阳性细胞的百分比以及膜和胞质染色的强度。激素受体、HER 2状态、B细胞淋巴瘤2（bcl-2）蛋白表达和蛋白p53的结果在组织病理学报告中报告为阳性或阴性，未进一步定量。结果：24.8%的患者检出CTC。具有上皮CTC的患者在CTC上的ANXA 2表达显著高于不具有CTC的患者（p=0.01）。CTCs与ANXA 2蛋白表达无相关性。然而，与不存在EMT CTC的患者相比，检测到具有EMT表型的CTC的患者在肿瘤基质中具有更高的ANXA 2表达（p=0.04）。激素阴性肿瘤的肿瘤细胞中ANXA 2表达显著高于激素阳性肿瘤（p=0.03）。类似地，与bcl-2阳性的肿瘤细胞相比，没有bcl-2蛋白表达的肿瘤具有更高的ANXA 2肿瘤水平（p=0.05）。结论：ANXA 2基质表达可能在与EMT CTC释放增加相关的侵袭性肿瘤表型中起关键作用，然而，ANXA 2以外的其他因素负责乳腺癌患者中CTC介导的凝血激活。
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.