Circulating tumor cell enumeration with a combination of epithelial cell adhesion molecule- and cell-surface vimentin-based methods for monitoring breast cancer therapeutic response.
Circulating tumor cell enumeration with a combination of epithelial cell adhesion molecule- and cell-surface vimentin-based methods for monitoring breast cancer therapeutic response.
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DOI：
10.1373/clinchem.2014.228122
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发表时间：
2015-01
影响因子：
9.3
通讯作者：
Li S
中科院分区：
文献类型：
--
作者：
Satelli A;Brownlee Z;Mitra A;Meng QH;Li S
从癌症患者中检测、分离和计数循环肿瘤细胞（CTC）已成为乳腺癌患者临床管理的重要模式。尽管CellSearch（一种用于分离上皮CTC的基于EpCAM的方法）已经获得了巨大的重要性，但其无法检测来自乳腺癌患者的间充质CTC引起了对其作为临床管理工具的实用性的担忧。为了解决这一技术差距，我们最近发现了细胞表面波形蛋白（CSV）作为检测肉瘤肿瘤间充质CTC的标志物的实用性。在本研究中，我们使用84-1（针对CSV的mAb，用于检测上皮间充质转化的CTC）和CellSearch方法，测试了在治疗期间从58名转移性乳腺癌患者中的每一名患者随机采集的血液中检测CTC的灵敏度和特异性。此外，我们测试了使用额外参数提高检测的灵敏度和特异性的可能性，所述额外参数包括细胞核EpCAM定位和上皮间质比率。与CellSearch方法相比，使用CSV的CTC计数在区分治疗应答（稳定）和治疗无应答（进展）人群方面具有显著性。结果还表明，如通过ROC曲线确定的，与其他测试组合相比，从两种方法检测到的CTC的总和（阈值为8个CTC/7.5mL）显著增加了CTC检测的特异性。总的来说，利用CellSearch和CSV方法的总和为使用CTC计数评估治疗反应提供了新的见解，从而为乳腺癌患者的个性化药物提供了新的方法。
Detection, isolation and enumeration of circulating tumor cells (CTCs) from cancer patients has become an important modality in clinical management of patients with breast cancer. Although CellSearch, an EpCAM based method that is used to isolate epithelial CTCs has gained immense importance, its inability to detect mesenchymal CTCs from breast cancer patients raises concerns for its utility as a clinical management tool. To address this gap in technology, we recently discovered the utility of cell-surface vimentin (CSV) as a marker for detecting mesenchymal CTC from sarcoma tumors. Here in this study, we tested the sensitivity and specificity of detecting CTC from blood collected at a random time during therapy from each of the 58 patients with metastatic breast cancer utilizing 84-1 (mAb against CSV to detect epithelial mesenchymal transitioned CTC) and CellSearch methods. Also we tested the possibility of improving the sensitivity and specificity of detection using additional parameters including nuclear EpCAM localization and epithelial mesenchymal ratios. CTC counts using CSV were significant in differentiating treatment responding (stable) and treatment non-responding (progression) populations in comparison to the CellSearch method. The results also indicated that a summation of CTCs detected from both methods with a threshold of 8 CTCs/7.5mL increased the specificity of CTC detection substantially in comparison with other tested combinations as determined by ROC curves. Collectively, utilizing a summation of CellSearch and CSV methods provide new insights into using CTC enumeration to assess therapeutic response and thus provides a new approach to personalized medicine in breast cancer patients.
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影响因子：
158.5
作者：
Cristofanilli, M;Budd, GT;Hayes, DF
通讯作者：
Hayes, DF
影响因子：
11.5
作者：
Riethdorf, Sabine;Fritsche, Herbert;Pantel, Klaus
通讯作者：
Pantel, Klaus
DOI：
10.1126/science.1228522
发表时间：
2013-02-01
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Yu M;Bardia A;Wittner BS;Stott SL;Smas ME;Ting DT;Isakoff SJ;Ciciliano JC;Wells MN;Shah AM;Concannon KF;Donaldson MC;Sequist LV;Brachtel E;Sgroi D;Baselga J;Ramaswamy S;Toner M;Haber DA;Maheswaran S
通讯作者：
Maheswaran S
影响因子：
11.2
作者：
Sarrió, David;Rodriguez-Pinilla, Socorro Maria;Palacios, José
通讯作者：
Palacios, José
影响因子：
11.5
作者：
Riethdorf, Sabine;Mueller, Volkmar;Pantel, Klaus
通讯作者：
Pantel, Klaus