Isolation and Characterization of Circulating Tumor Cells from Patients with Localized and Metastatic Prostate Cancer

作者：Shannon L. Stott, Richard J. Lee, Sunitha Nagrath, Min Yu, David T. Miyamoto, Lindsey Ulkus, Elizabeth K. Inserra, Matthew Ulman, Simeon Springer, Zev M. Nakamura, Alessandra L. Moore, Dina Tsukrov, Maria E. Kempner, Douglas M. Dahl, Chin‐Lee Wu, A. John Iafrate, Matthew R. Smith, Ronald G. Tompkins, Lecia V. Sequist, Mehmet Toner, Daniel A. Haber, Shyamala Maheswaran · 发表于：Science Translational Medicine · 年份：2010 · DOI：10.1126/scitranslmed.3000403 · 被引用次数：539 · 研究领域：Cancer Cells and Metastasis、Prostate Cancer Treatment and Research、Cancer Genomics and Diagnostics

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 indica...