Cell-free tumor DNA in blood plasma as a marker for circulating tumor cells in prostate cancer.
OBJECTIVE
Circulating cell-free DNA in the blood of cancer patients harbors tumor-specific aberrations. Here, we investigated whether this DNA might also reflect the presence of circulating tumor cells (CTC).


METHODS
To identify the source of cell-free DNA in blood, plasma derived from 81 patients with prostate cancer was examined for CTCs and cell-free DNA. An epithelial immunospot assay was applied for detection of CTCs, and a PCR-based fluorescence microsatellite analysis with a panel of 14 polymorphic markers was used for detection of allelic imbalances (AI).


RESULTS
The plasma DNA levels significantly correlated with the diagnosis subgroups of localized (stage M0, n = 69) and metastasized prostate cancer (stage M1, n = 12; P = 0.03) and with the tumor stage of these patients (P < 0.005). AI was found on cell-free DNA in plasma from 45.0% and 58.5% of M0 and M1 patients, respectively. Detection of CTCs showed that 71.0% or 92.0% of the M0 and M1 patients harbored 1 to 40 CTCs in their blood, respectively. The occurrence of CTCs correlated with tumor stage (P < 0.03) and increasing Gleason scores (P = 0.04). Notably, significant associations of the number of CTCs with the AI frequencies at the markers D8S137 (P = 0.03), D9S171 (P = 0.04), and D17S855 (P = 0.02) encoding the cytoskeletal protein dematin, the inhibitor of the cyclin-dependent kinase CDKN2/p16 and BRCA1, respectively, were observed.


CONCLUSIONS
These findings show, for the first time, a relationship between the occurrence of CTCs and circulating tumor-associated DNA in blood, which, therefore, might become a valuable new source for monitoring metastatic progression in cancer patients.
Schwarzenbach
Heidi
H
Institute of Tumor Biology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. hschwarz@uke.uni-hamburg.de
Alix-Panabières
Catherine
C
Müller
Imke
I
Letang
Nicolas
N
Vendrell
Jean-Pierre
JP
Rebillard
Xavier
X
Pantel
Klaus
K
D022981:Allelic Imbalance; D014408:Biomarkers, Tumor / Q000097:blood; D002474:Cell-Free System; D004273:DNA, Neoplasm / Q000032:analysis*; D006801:Humans; D008297:Male; D009362:Neoplasm Metastasis / Q000175:diagnosis; D009360:Neoplastic Cells, Circulating; D010949:Plasma; D011110:Polymorphism, Genetic; D011471:Prostatic Neoplasms / Q000097:blood* / Q000235:genetics* / Q000473:pathology; D012307:Risk Factors
D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm