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Murray Primary circulating prostate cells

and their presence was associated with a worse detection rate of 20% in men with cancer and in 21% of
prognosis. However, there is no consensus regarding men with a benign prostatic disease. Using the same
[86]
the morphologic characteristics necessary to define CellSearch system Thalgott et al. failed to detect
[87]
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cell clusters using the CellSearch system. a difference between men with localized prostate
cancer and healthy controls. Using RT-PCR, only 8%
RT-PCR detection of circulating tumor cells of men with localized prostate cancer were positive for
RT-PCR is a more sensitive method than circulating tumor cells, and the results were concordant
immunocytochemistry to detect circulating tumor with the use of the CellSearch system. In men with
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[88]
cells. However, it has its limitations in that; (1) there high risk non-metastatic prostate cancer and prior to
may be amplification of nonspecific gene products; any therapy, 14% of men had circulating tumor cells
(2) it lacks thoroughly validated protocols for sample detected. [89]
processing, RNA-preparation, cDNA synthesis, and
PCR conditions; (3) it lacks rigorous quality control In contrast, using the MetaCell system, circulating
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measures on a per-sample basis (the lack of a tumor cells were identified in 52% of men with
validated method increases the possibility of variations localized prostate cancer, while Stott et al. using
[90]
[91]
in sensitivity, specificity, and the potential of nonspecific a CTC chip platform detected circulating tumor cells
amplification products being detected); and (4) there is with a cut-off value of ≥ 14 to determine a positive test
no morphological confirmation of tumor cells. found 42% of men with localized prostate cancer to be
positive. However, using a telomerase-based method
The number of articles describing single or multiple Fizazi et al. detected tumor cells in 79% of men with
[92]
markers to characterize CTCs using RT-qPCR in localized prostate cancer. Using a combination of PSA
the blood of cancer patients has increased greatly and P504S immunocytochemistry, a study of over
in recent years, especially in breast cancer. [81-85] 1,000 men undergoing prostate biopsy for an elevated
The Adnatest PC CTC platform consists of the PSA reported that 35% of men were CPC positive;
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ProstateCancerSelect and ProstateCancerDetect used as a sequential test after PSA screening, it
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system. The ProstateCancerSelect system allows showed a sensitivity of 81%, specificity of 89%, and
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for an enrichment of tumor cells by an antibody- a negative predictive value of 90%. The same
[93]
mix (anti-EpCAM, anti-Her2) linked to magnetic group compared this method of CPC detection with
particles and mRNA isolated from the selected cells. PSA kinetics, age-defined PSA cut-off values, and the
The ProstateCancerDetect System transcribes the Montreal nomogram, and reported that CPC detection
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isolated mRNA into cDNA, and a multiplex PCR is was superior in predicting prostate cancer at first
performed for the analysis of tumor-associated gene biopsy. [94-96] They also concluded that men with low-
expression (PSA, PSMA, EGFR). The use of multiplex grade small volume tumors, those complying with the
systems permits an increased characterization of criteria for active observation, were CPC negative.
[97]
circulating tumor cells. Men with benign prostatic disease, especially
Cell clusters cannot be detected using methods of Table 1: Enrichment and detection systems of commercially
RT-PCR. Enumeration systems are normally imaged available kits
based, using immunocytochemistry or laser scanning System Enrichment Detection
techniques. Table 1 shows a summary of each CellSearch IC EpCAM IF CK, CD45, DAPI
commercial CTC detection kit. Epispot IC non-EpCAM Secretion of proteins
CK19, MUC1, PSA
Metacell Cell size ICC for CK
CLINICAL USE OF THE DETECTION OF CTC membrane Cell size IF for CK
PRIMARY CPCS RosetteSep ID CD45 IF for CK EpCAM CD45
Microfluids and IC
IF for CK EpCAM CD45
Nanovelcro chip
Adnatest IC EpCAM qRT-PCR
In the detection of prostate cancer Ficoll-Paque Cell density ICC PSA and P504S
There are few reported studies of the use of circulating IC: immune-capture; IF: immunofluorescence; CK: cytokeratin;
ICC: immunocytochemistry; ID: immune-depletion; PSA: prostate-
tumor cells to detect prostate cancer. Early studies specific antigen
using different detection methods compared the
presence of these cells in healthy controls, men with Table 2: Methods reported in the detection and pretreatment
localized cancer, and men with metastatic prostate prognosis of prostate cancer
cancer. Circulating tumor cells appear to be less Diagnosis Prognosis
frequently detected in men with localized prostate CellSearch Not useful Not useful
Rt-PCR
Not useful
Possibly useful
cancer than those patients with advanced or metastatic Ficol-Paque Possibly useful Possibly useful
cancer. In men with an increased PSA, there was a Rt-PCR: reverse transcriptase-polymerase chain reaction
458 Journal of Cancer Metastasis and Treatment ¦ Volume 2 ¦ December 16, 2016