Isolation and characterization of circulating tumor cells from patients with localized and metastatic prostate cancer.
Isolation and characterization of circulating tumor cells from patients with localized and metastatic prostate cancer.
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DOI：
10.1126/scitranslmed.3000403
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发表时间：
2010-03-31
影响因子：
17.1
通讯作者：
Maheswaran S
中科院分区：
文献类型：
--
作者：
Stott SL;Lee RJ;Nagrath S;Yu M;Miyamoto DT;Ulkus L;Inserra EJ;Ulman M;Springer S;Nakamura Z;Moore AL;Tsukrov DI;Kempner ME;Dahl DM;Wu CL;Iafrate AJ;Smith MR;Tompkins RG;Sequist LV;Toner M;Haber DA;Maheswaran S
罕见的循环肿瘤细胞（CTC）存在于转移性上皮癌患者的血液中，但难以常规测量。我们报告了一种利用前列腺特异性抗原（PSA）（一种独特的前列腺肿瘤相关标志物）分析前列腺CTC的定量自动成像系统。PSA染色的特异性使得能够优化基线图像强度、形态测量和三维微流体装置中多个信号的整合的标准。在一项初步分析中，我们在19名患者中的8名（42%）手术切除肿瘤之前检测了患有局部疾病的前列腺癌患者的CTC（范围为38至222个CTC/毫升）。对于8名术前患有CTC的患者中的6名，术后急剧下降（<24小时）表明CTC在血液循环中的半衰期较短。其他患者在前列腺切除后持续CTC长达3个月，表明早期但短暂的播散性肿瘤沉积。在转移性前列腺癌患者中，36例中有23例（64%）检测到CTC（范围为14至5000个CTC/ml）。在既往未接受治疗的患者中，纵向随访发现，在开始有效治疗后，CTC的数量下降。前列腺癌特异性TMPRSS 2-ERG融合在从20名（45%）患有转移性疾病的患者中的9名的CTC提取的RNA中是可检测的，并且捕获的CTC的PSA和细胞分裂标志物Ki 67的双重染色指示CTC中增殖细胞的比例的宽范围。这种用于分析CTC的方法将促进非侵入性肿瘤采样在晚期前列腺癌中的直接靶向治疗的应用，并保证启动长期临床研究以测试CTC在侵入性局部疾病中的重要性。
Rare circulating tumor cells (CTCs) are present in the blood of patients with metastatic epithelial cancers but have been difficult to measure routinely. We report a quantitative automated imaging system for analysis of prostate CTCs, taking advantage of prostate-specific antigen (PSA), a unique prostate tumor–associated marker. The specificity of PSA staining enabled optimization of criteria for baseline image intensity, morphometric measurements, and integration of multiple signals in a three-dimensional microfluidic device. In a pilot analysis, we detected CTCs in prostate cancer patients with localized disease, before surgical tumor removal in 8 of 19 (42%) patients (range, 38 to 222 CTCs per milliliter). For 6 of the 8 patients with preoperative CTCs, a precipitous postoperative decline (<24 hours) suggests a short half-life for CTCs in the blood circulation. Other patients had persistent CTCs for up to 3 months after prostate removal, suggesting early but transient disseminated tumor deposits. In patients with metastatic prostate cancer, CTCs were detected in 23 of 36 (64%) cases (range, 14 to 5000 CTCs per milliliter). In previously untreated patients followed longitudinally, the numbers of CTCs declined after the initiation of effective therapy. The prostate cancer–specific TMPRSS2-ERG fusion was detectable in RNA extracted from CTCs from 9 of 20 (45%) patients with metastatic disease, and dual staining of captured CTCs for PSA and the cell division marker Ki67 indicated a broad range for the proportion of proliferating cells among CTCs. This method for analysis of CTCs will facilitate the application of noninvasive tumor sampling to direct targeted therapies in advanced prostate cancer and warrants the initiation of long-term clinical studies to test the importance of CTCs in invasive localized disease.
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影响因子：
11.2
作者：
Attard, Gerhardt;Swermenhuis, Joost F.;de Bono, Johann S.
通讯作者：
de Bono, Johann S.
影响因子：
7.5
作者：
Mehra, Rohit;Tomlins, Scott A.;Shah, Rajal B.
通讯作者：
Shah, Rajal B.
影响因子：
11.2
作者：
Gopalan A;Leversha MA;Satagopan JM;Zhou Q;Al-Ahmadie HA;Fine SW;Eastham JA;Scardino PT;Scher HI;Tickoo SK;Reuter VE;Gerald WL
通讯作者：
Gerald WL
影响因子：
11.5
作者：
Danila, Daniel C.;Heller, Glenn;Scher, Howard I.
通讯作者：
Scher, Howard I.
影响因子：
50.5
作者：
Olmos, D.;Arkenau, H. -T.;de Bono, J. S.
通讯作者：
de Bono, J. S.