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precision and subpopulation quantifi cation with high fully clarifi ed when compared with corresponding tumors
specifi city due to simultaneous analysis using multiple in GI cancer. The molecular and genetic characteristics
parameters. However, in contrast to RT-PCR technique, of CTCs are usually analyzed by PCR-based methods,
the disadvantage of this technique has a lower sensitivity. fl uorescent in situ hybridization (FISH) or comparative
genomic hybridization (CGH). There have been no
Fiber-optic Array Scanning Technology, a rapid and accurate reports about CTCs characterization analyzed by FISH
CTC location cytometric system, is a scanning technology and CGH in gastric cancer, whereas abnormal copy
characterized by a large fi eld of view. It allows analyzing number alteration was detected in CTCs from patients
[19]
large volumes of samples without any purifi cation step and with metastatic prostate cancer. [25-27] Using PCR-based
minimizing the risk of cell loss. Additional scanning systems methods, conventional detection system with epithelial
such as ACIS (Automated Cellular Imaging System, DAKO, markers such as CEA and CK has been previously
Spatial Technology, USA) and ARIOL (Applied Imaging performed to show the clinical signifi cance of CTCs in
Corp, Wetzlar, Germany) are available on the market.
gastric cancer. [28-32] However, Mimori et al. showed in a
[33]
Recent Advances in Detection of Circulating large-scale study that CTCs circulate even in early stages
Tumor Cells of the disease indicating that the simultaneous presence
of CTC and VEGFR-1 expression is clinically signifi cant
As discussed above, the detection of CTCs is involved for disease progression. It is also well known that there
in two steps of enrichment and identifi cation; thus, the is discordance of expression profi le between CTCs
development of automated techniques could offer at and primary tumor, and several markers for regulating
the same time enrichment, staining and scanning of the metastasis and prognosis have been determined by
samples. The Cell Search System® enriches the CTCs PCR-based methods. [34-37] Furthermore, a comprehensive
with ferrofl uid nanoparticles coated with anti-EpCAM molecular profi ling using the cDNA microarray was
antibody. The enriched EpCAM+ population is stained with performed to identify novel genes to predict gastric
phycoerythrin-conjugated antibodies against CK-8, -18 cancer metastasis, recurrence and prognosis, suggesting
and -19 with all ophycocyanin-conjugated antibodies that expression of MT1-MMP in peripheral blood
specifi c for leukocytes (anti-CD45 antibody) and with the identifi ed by the cDNA microarray technique in gastric
nuclear dye 4’, 6-diamino-2-phenylidole (DAPI) for the cancer was a powerful indicator of distant metastasis,
+
nucleic acids staining. The CK /DAPI /CD45 cells are especially for peritoneal dissemination. van de
+
−
[38]
then counted as CTCs using CellSpotter analyzer (Veridex, Stolpe et al. reported that CTCs were heterogeneous
[39]
Warren, NJ), a four-color semi-automated fl uorescent and differed among different cancer types. In addition to
microscope. More recently, CTC-chip based on a differences across cancer types, CTCs have heterogeneity
[20]
microfl uidic platform has also developed to isolate a high within the same patient. Although the heterogeneity of
rate of CTCs. CTC-chip consists of an array of 78,000 primary tumors has been known, Klein et al. showed
[21]
microspots coated with anti-EpCAM antibodies. Whole that early disseminated cancer cells are genomically
blood is pumped through this chip, and EpCAM+ cells very unstable, as well as the primary tumor. In this
[40]
are captured and detected by cameras identifying their case, gastric cancer is well known to have histological
morphology, viability and the expressions of tumor heterogeneity in primary lesion. Various histological types
markers. However, the relevance of this technology in and differentiation of gastric cancer cells are frequently
[14]
clinical setting remains unclear and clinical validation study observed in the same specimens. Therefore, histological
[41]
is required. Finally, based on enzyme-linked immunospot heterogeneity may make it diffi cult to the molecular and
assay technology, epithelial immunospot (EPISPOT) assay genetic characterization of CTCs in GI cancer.
can identify CTCs by detecting specifi c CTC-secreted
proteins (CK, mucin or prostate specifi c antigen). [22,23] Clinical Relevance of Circulating Tumor Cells
EPISPOT makes it possible to detect the only viable CTCs in Gastrointestinal Cancer
because dying CTCs are unable to secrete an adequate To date, there are a number of methodologies in the
amount of proteins to be detected. Sensitivity of EPISPOT detection of CTCs and the clinical relevance of GI cancer
is superior to ELISA assay in a two-order magnitude while have been reported. In clinical setting, the detection
detecting the release of CK-19 from tumor cells. [24] of CTC is expected to be useful in early diagnosis
Recent Development of Molecular and Genetic of cancer, monitoring of treatment responses and
Characterization of Circulating Tumor Cells disease progression. In the following, we summarized
a comprehensive update of the studies with more than
The next desirable step is to elucidate the molecular and 50 patients or with an outcome analysis and discussed
genetic characterization of CTCs after enrichment and their clinical implications in selected GI cancers.
isolation of CTCs. This step may help us to comprehend
the mechanism of cancer metastasis, leading to the Esophageal cancer
development of treatments of tumor metastasis. However, There are only a few studies of esophageal cancer
the molecular and genetic characteristics of CTCs are not available as compared to gastric and colorectal cancers

132 Journal of Cancer Metastasis and Treatment ¦ Volume 1 ¦ Issue 3 ¦ October 15, 2015 ¦