In patients with metastatic breast cancer the identification of circulating tumor cells in epithelial-to-mesenchymal transition is associated with a poor prognosis.
In patients with metastatic breast cancer the identification of circulating tumor cells in epithelial-to-mesenchymal transition is associated with a poor prognosis.
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在转移性乳腺癌的患者中，上皮到间质转变中循环肿瘤细胞的鉴定与预后不良有关。
DOI：
10.1186/s13058-016-0687-3
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发表时间：
2016-03-09
期刊：
影响因子：
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通讯作者：
Cesselli D
中科院分区：
文献类型：
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作者：
Bulfoni M;Gerratana L;Del Ben F;Marzinotto S;Sorrentino M;Turetta M;Scoles G;Toffoletto B;Isola M;Beltrami CA;Di Loreto C;Beltrami AP;Puglisi F;Cesselli D
虽然最近的模型表明，在上皮间质转化（EM CTC）中检测循环肿瘤细胞（CTC）可能与转移性乳腺癌（MBC）患者的疾病进展有关，但目前的检测方法在识别这种细胞亚群方面并不有效。此外，EM CTC与MBC患者的临床病理特征和预后的可能关联仍有待证实。本研究的目的是：首先，优化基于DEPArray的协议，该协议旨在识别、量化和分类单个可行的EM CTC，随后测试EM CTC频率与临床数据的关联。这项前瞻性观察性研究入组了56例MBC患者，不考虑治疗线。用识别上皮和间充质标志物的抗体混合物对去除了CD 45 pos白细胞的血液样品进行染色。鉴定了四种CD 45阴性细胞亚群：仅表达上皮标志物的细胞（E CTC）、共表达上皮和间充质标志物的细胞（EM CTC）、仅表达间充质标志物的细胞（MES）和对每种测试标志物呈阴性的细胞（NEG）。将CTC亚群定量为绝对细胞计数和相对频率。分别通过Wilcoxon-Mann-Whitney检验和单变量考克斯回归分析探讨CTC亚群与临床病理特征、无进展生存期（PFS）和总生存期（OS）的相关性。通过采用基于DEPAray的策略，我们能够评估每个MBC患者中属于上述类别的细胞的存在。我们观察到特异性CD 45阴性亚群与肿瘤亚型（例如NEG和三阴性）、增殖（NEG和Ki 67表达）和转移扩散部位（例如ECTC和骨; NEG和脑）之间存在显著相关性。重要的是，共表达上皮和间充质标志物（EM CTC）的CD 45阴性细胞的分数与较差的PFS和OS显著相关，后者是根据IV期疾病的诊断和初始CTC评估计算的。这项研究表明，在MBC中解剖CTC的异质性的重要性。CTC的精确表征有助于估计转移模式和结果，推动临床决策和监测策略。本文的在线版本（doi：10.1186/s13058-016-0687-3）包含补充材料，可供授权用户使用。
Although recent models suggest that the detection of Circulating Tumor Cells (CTC) in epithelial-to-mesenchymal transition (EM CTC) might be related to disease progression in metastatic breast cancer (MBC) patients, current detection methods are not efficient in identifying this subpopulation of cells. Furthermore, the possible association of EM CTC with both clinicopathological features and prognosis of MBC patients has still to be demonstrated. Aims of this study were: first, to optimize a DEPArray-based protocol meant to identify, quantify and sort single, viable EM CTC and, subsequently, to test the association of EM CTC frequency with clinical data. This prospective observational study enrolled 56 MBC patients regardless of the line of treatment. Blood samples, depleted of CD45pos leukocytes, were stained with an antibody cocktail recognizing both epithelial and mesenchymal markers. Four CD45neg cell subpopulations were identified: cells expressing only epithelial markers (E CTC), cells co-expressing epithelial and mesenchymal markers (EM CTC), cells expressing only mesenchymal markers (MES) and cells negative for every tested marker (NEG). CTC subpopulations were quantified as both absolute cell count and relative frequency. The association of CTC subpopulations with clinicopathological features, progression free survival (PFS), and overall survival (OS) was explored by Wilcoxon-Mann-Whitney test and Univariate Cox Regression Analysis, respectively. By employing the DEPArray-based strategy, we were able to assess the presence of cells pertaining to the above-described classes in every MBC patient. We observed a significant association between specific CD45neg subpopulations and tumor subtypes (e.g. NEG and triple negative), proliferation (NEG and Ki67 expression) and sites of metastatic spread (e.g. E CTC and bone; NEG and brain). Importantly, the fraction of CD45neg cells co-expressing epithelial and mesenchymal markers (EM CTC) was significantly associated with poorer PFS and OS, computed, this latter, both from the diagnosis of a stage IV disease and from the initial CTC assessment. This study suggests the importance of dissecting the heterogeneity of CTC in MBC. Precise characterization of CTC could help in estimating both metastatization pattern and outcome, driving clinical decision-making and surveillance strategies. The online version of this article (doi:10.1186/s13058-016-0687-3) contains supplementary material, which is available to authorized users.