Expression of stem cell and epithelial-mesenchymal transition markers in primary breast cancer patients with circulating tumor cells.
Expression of stem cell and epithelial-mesenchymal transition markers in primary breast cancer patients with circulating tumor cells.
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DOI：
10.1186/bcr3099
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发表时间：
2012-01-20
期刊：
影响因子：
--
通讯作者：
Fehm T
中科院分区：
文献类型：
--
作者：
Kasimir-Bauer S;Hoffmann O;Wallwiener D;Kimmig R;Fehm T
乳腺癌中循环肿瘤细胞（CTC）的存在可能与干细胞样肿瘤细胞有关，干细胞样肿瘤细胞被认为是原发肿瘤转移扩散的活跃来源。此外，为了能够扩散和转移，CTC必须能够进行上皮-间质转化（EMT）。我们研究了502例原发性乳腺癌患者CTC中三种EMT标志物和干细胞标志物ALDH 1的表达。数据与骨髓（BM）中弥散性肿瘤细胞（DTC）的存在以及患者的临床病理数据相关。使用AdnaTest BreastCancer（AdnaGen AG）分析总计2 × 5 ml血液的CTC，以检测EpCAM、MUC-1、HER 2和β-肌动蛋白转录物。另外，对回收的c-DNA进行三种EMT标志物[TWIST 1、Akt 2、磷酸肌醇激酶-3（PI 3 K α）]的多重检测，并分别检测肿瘤干细胞标志物ALDH 1。如果在样品中检测到至少一种标志物，则认为EMT标志物鉴定为阳性。使用泛细胞角蛋白抗体A45-B/B3通过免疫细胞化学分析来自所有患者的两个BM抽吸物的DTC。在调查的30份健康捐献者样本中，97%的EMT呈阴性，95%的ALDH 1转录本呈阴性。在97/502例（19%）患者中检测到CTC。至少有一种EMT标记物在29%的样本中表达，ALDH 1在14%的样本中存在。有趣的是，基于应用AdnaTest BreastCancer确定的CTC阳性截止水平，5%的ALDH 1阳性患者和18%的EMT阳性患者为CTC阴性。在107/502例（21%）患者中检测到BM中的DTC，未发现BM状态与CTC阳性之间的相关性（P = 0.41）。CTC、EMT和ALDH 1表达的存在与任何预后临床标志物均不相关。我们的数据表明：（1）一部分原发性乳腺癌患者表现出EMT和干细胞特征，（2）目前使用的CTC检测方法无法有效识别经历EMT的CTC亚型。(3)预后和治疗反应的临床相关性必须在前瞻性试验中进一步评估。
The presence of circulating tumor cells (CTC) in breast cancer might be associated with stem cell-like tumor cells which have been suggested to be the active source of metastatic spread in primary tumors. Furthermore, to be able to disseminate and metastasize, CTC must be able to perform epithelial-mesenchymal transition (EMT). We studied the expression of three EMT markers and the stem cell marker ALDH1 in CTC from 502 primary breast cancer patients. Data were correlated with the presence of disseminated tumor cells (DTC) in the bone marrow (BM) and with clinicopathological data of the patients. A total of 2 × 5 ml of blood was analyzed for CTC with the AdnaTest BreastCancer (AdnaGen AG) for the detection of EpCAM, MUC-1, HER2 and beta-Actin transcripts. The recovered c-DNA was additionally multiplex tested for three EMT markers [TWIST1, Akt2, phosphoinositide kinase-3 (PI3Kα)] and separately for the tumor stem cell marker ALDH1. The identification of EMT markers was considered positive if at least one marker was detected in the sample. Two BM aspirates from all patients were analyzed for DTC by immunocytochemistry using the pan-cytokeratin antibody A45-B/B3. Ninety-seven percent of 30 healthy donor samples investigated were negative for EMT and 95% for ALDH1 transcripts, respectively. CTC were detected in 97/502 (19%) patients. At least one of the EMT markers was expressed in 29% and ALDH1 was present in 14% of the samples, respectively. Interestingly, 5% of the ALDH1-positive and 18% of the EMT-positive patients were CTC-negative based on the cut-off level determined for CTC-positivity applying the AdnaTest BreastCancer. DTC in the BM were detected in 107/502 (21%) patients and no correlation was found between BM status and CTC positivity (P = 0.41). The presence of CTC, EMT and ALDH1 expression was not correlated to any of the prognostic clinical markers. Our data indicate that (1) a subset of primary breast cancer patients shows EMT and stem cell characteristics and (2) the currently used detection methods for CTC are not efficient to identify a subtype of CTC which underwent EMT. (3) The clinical relevance on prognosis and therapy response has to be further evaluated in a prospective trial.
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DOI：
10.1186/bcr2349
发表时间：
2009
期刊：
Breast cancer research : BCR
影响因子：
--
作者：
Fehm T;Hoffmann O;Aktas B;Becker S;Solomayer EF;Wallwiener D;Kimmig R;Kasimir-Bauer S
通讯作者：
Kasimir-Bauer S
影响因子：
158.5
作者：
Cristofanilli, M;Budd, GT;Hayes, DF
通讯作者：
Hayes, DF
影响因子：
64.5
作者：
Gupta PB;Onder TT;Jiang G;Tao K;Kuperwasser C;Weinberg RA;Lander ES
通讯作者：
Lander ES
DOI：
10.1093/jnci/djj267
发表时间：
2006-07-19
期刊：
JOURNAL OF THE NATIONAL CANCER INSTITUTE
影响因子：
--
作者：
Asselin-Labat, Marie-Liesse;Shackleton, Mark;Lindeman, Geoffrey J.
通讯作者：
Lindeman, Geoffrey J.
DOI：
10.1097/igc.0b013e318216cb91
发表时间：
2011-07-01
影响因子：
4.8
作者：
Aktas, Bahriye;Kasimir-Bauer, Sabine;Wimberger, Pauline
通讯作者：
Wimberger, Pauline