title: Isolation and characterization of circulating tumor cells from patients with localized and metastatic prostate cancer.
abstract: 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.
authors.affiliation: Center for Engineering in Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
authors.forename: Shannon L
authors.initials: SL
authors.lastname: Stott
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Lee
authors.forename: Sunitha
authors.initials: S
authors.lastname: Nagrath
authors.forename: Min
authors.initials: M
authors.lastname: Yu
authors.forename: David T
authors.initials: DT
authors.lastname: Miyamoto
authors.forename: Lindsey
authors.initials: L
authors.lastname: Ulkus
authors.forename: Elizabeth J
authors.initials: EJ
authors.lastname: Inserra
authors.forename: Matthew
authors.initials: M
authors.lastname: Ulman
authors.forename: Simeon
authors.initials: S
authors.lastname: Springer
authors.forename: Zev
authors.initials: Z
authors.lastname: Nakamura
authors.forename: Alessandra L
authors.initials: AL
authors.lastname: Moore
authors.forename: Dina I
authors.initials: DI
authors.lastname: Tsukrov
authors.forename: Maria E
authors.initials: ME
authors.lastname: Kempner
authors.forename: Douglas M
authors.initials: DM
authors.lastname: Dahl
authors.forename: Chin-Lee
authors.initials: CL
authors.lastname: Wu
authors.forename: A John
authors.initials: AJ
authors.lastname: Iafrate
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Smith
authors.forename: Ronald G
authors.initials: RG
authors.lastname: Tompkins
authors.forename: Lecia V
authors.initials: LV
authors.lastname: Sequist
authors.forename: Mehmet
authors.initials: M
authors.lastname: Toner
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Haber
authors.forename: Shyamala
authors.initials: S
authors.lastname: Maheswaran
mesh_terms: D003952:Diagnostic Imaging; D005260:Female; D006801:Humans; D008297:Male; D009360:Neoplastic Cells, Circulating / Q000378:metabolism* / Q000473:pathology*; D017430:Prostate-Specific Antigen / Q000097:blood / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology*
chemical_list: D017430:Prostate-Specific Antigen