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alone can not be a predictor of cancer metastasis in a was the fi rst CTC detection system that was approved
large-scale study. This study also revealed that elevated by US FDA. Furthermore, a previous meta-analysis
[2]
expression of VEGFR-1 facilitated the establishment of reported the aprognostic signifi cance of CTC detected
[48]
®
hematogenous metastases of gastric cancer and that the by the CellSearch System has been reported. Eleven
simultaneous presence of CTC and VEGFR-1 expression studies including 1,847 colorectal cancer patients were
at premetastatic sites was clinically signifi cant in disease analyzed in this study and the presence of CTCs was
progression. signifi cantly associated with overall and progression-free
survival as reported by the previous meta-analysis. In
[52]
Colorectal cancer
a previous prospective study of non-metastatic colorectal
To date, there are a large number of studies of CTC cancer, preoperative CTC detection was a strong
detection in colorectal cancer as compared to other and independent prognostic marker. The treatment
[53]
GI cancers as summarized in Table 3. RT-PCR and the response rate was signifi cantly lower in CTC-positive
CellSearch System have been mainly reported methods patients than that of CTC negative patients at base line
®
to detect CTC in colorectal cancer and data showed that and during treatment. [23,54-57] Another previous study
CTCs were associated recurrence and overall survival of demonstrated potentially clinical application in detection
patients. For example, Cohen et al. revealed that the of KRAS mutational in CTCs for selecting metastatic
[2]
[58]
®
number of CTCs detected by the CellSearch System colorectal cancer patients for cetuximab therapy. In
before and during treatment was an independent addition, recent development of molecular and genetic
predictor of PFS and OS in 430 patients with metastatic characterization of single-CTC demonstrated that there
colorectal cancer in a prospective multicenter clinical was intra- and inter- heterogeneity of EGFR expression
trial. The CellSearch System using in colorectal cancer and genetic alterations of EGFR, KRAS and PIK3CA,
®
Table 3: Clinical relevance of CTC in colorectal cancer
Author Year Case Method Molecuar marker Clinical relevance
Wong 2009 132 ICC CK-20 Predictive marker for OS
Tanigich 2000 53 RT-PCR CEA Predictive marker for DFS
Yamagichi 2000 52 RT-PCR CK-20, CEA Shorter OS
Hardingham 2000 94 RT-PCR CK-19, 20, MUC2 Shorter DFS
Bessa 2001 68 RT-PCR CEA No prognostic impact
Ito 2002 99 RT-PCR CEA Shorter DFS
Bessa 2003 66* RT-PCR CEA No prognostic impact
Sadahiro 2005 93 RT-PCR CEA No prognostic impact
Koch 2006 90 RT-PCR CK-20 Shorter DFS
Douard 2006 121 RT-PCR CK-20, CGM2 No prognostic impact
Iinuma 2006 167 RT-PCR CK-20, CEA Shorter DFS and OS
Katsumata 2006 57 RT-PCR CK-20 Strong relation to LN metastais and OS
Allen-Mersh 2007 113* RT-PCR CK-20, CEA Shorter DFS
Wang 2007 157* RT-PCR** CK-19, 20, CEA, hTERT Shorter DFS
Uen 2007 194 RT-PCR** CK-19, 20, CEA, hTERT Shorter DFS
Sadahiro 2007 200* RT-PCR CEA Shorter DFS
Uen 2007 438* RT-PCR CK-19, 20, CEA, hTERT Shorter DFS
Yie 2008 86 RT-PCR, ELISA Survivin Predictive marker for DFS
Lu 2011 141* RT-PCR** CK-19, 20, CEA, hTERT Shorter DFS and OS
Iinuma 2011 735 RT-PCR CK-19, 20, CEA, hTERT Shorter DFS and OS
Pilati 2012 50 RT-PCR CK-19, 20, CEA, CD133, Predictive marker for OS (CD133 CTC)
VEGF, EGFR, Survivin
Cohen 2008 430 CellSearch EpCAM, CK-8, 18, 19 Predictive marker for OS (CTC ≥ 3)
Matsusaka 2011 64 CellSearch EpCAM, CK-8, 18, 19 Predictive marker for PFS and OS (CTC level after Cx)
Tol 2010 467 CellSearch EpCAM, CK-8, 18, 19 Predictive marker for PFS and OS (CTC level before Cx)
Sastre 2012 180 CellSearch EpCAM, CK-8, 18, 19 Predictive marker for PFS and OS (CTC level before Cx)
Aggarwal 2013 209 CellSearch EpCAM, CK-8, 18, 19 Predictive marker for OS (CTC level before Cx)
Gazzaniga 2013 119 CellSearch EpCAM, CK-8, 18, 19 Predictive marker for OS (CTC ≥ 1)
Kuboki 2013 63 CellSearch EpCAM, CK-8, 18, 19 Shorter DFS and OS
Sotelo 2015 472 CellSearch EpCAM, CK-8, 18, 19 No prognostic impact (stage III)
Seeberg 2015 194 CellSearch EpCAM, CK-8, 18, 19 Predict nonresectability and impaired survival
*Post-operative mesuament. **Membrane array. ICC: Immunocytochemistry; ELISA: Enzyme-Linked ImmunoSorbent Assay;
hTERT: Human Telomerase reverse transcriptase; LN: Lymphnode metastasis; DFS: Disease free survival; OS: Overall survival;
PFS: Progression free survival; Cx: Chemotherapy

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