180
metastatic phenotypes. This association is strengthened by the
findings by Reeh et al., where they have demonstrated that patients
with adenocarcinoma of the esophagus exhibit high levels (20% vs
10%) of CTCs when compared to patients with esophageal squa-
mous cell carcinomas [ 16 ]. Consistent with this hypothesis,
Driemel et al. have reported that epithelial cellular adhesion mol-
ecule (EpCAM), a key marker for the identification/isolation of
CTCs in peripheral blood, frequently expresses with esophageal
adenocarcinomas with metastasis [ 17 ]. Taken together, CTCs
could act as a biomarker for the prediction of cancer progression
and early detection metastasis in esophageal adenocarcinomas.
However, lack of CTC studies on the Western population with
esophageal adenocarcinomas and use of different methods for
CTC detection limit its generalized application for diagnostic and
treatment purpose.Previous studies have found that detecting the levels of CTCs in
the blood may provide useful information on tumor staging, prog-
nosis, and treatment outcomes [ 3 , 18 , 19 ]. Sclafani et al. reported
that amongst 11 patients with metastatic adenocarcinomas (two
from the esophagus and 9 from esophagogastric junction), those
having ≥2 CTCs in their peripheral blood showed a poor median
survival rate (6 months vs 10 months) when compared to those
with <2 CTCs [ 20 ]. However, this study was done along with gas-
tric adenocarcinomas and both patients with esophageal adenocar-
cinomas did not show ≥2 CTCs in their peripheral blood [ 20 ]. In
2015, Reeh et al. have examined the biomarker potential of CTCs
in a larger population of esophageal adenocarcinomas (n = 68) and
compared against CTCs in 29 patients with esophageal squamous
cell carcinomas [ 16 ]. This study has noted a significant difference
in CTC levels between squamous and adenocarcinomas. Half
(5/10) of the patients with adenocarcinoma having pathological T
stage showed CTC positive while no patient with esophageal squa-
mous cell carcinoma (0/3) showed any CTC positivity with the
similar stage. In addition, most of the patients with adenocarci-
noma having distant metastasis showed CTC positivity. Only one
patient with squamous cell carcinoma with distant metastasis did
not show any CTCs in their peripheral blood [ 16 ]. Similar to the
findings of Sclafani et al., Reeh and colleagues noted poor progno-
sis in patients with CTC- positive esophageal carcinomas. Analogues
findings were also reported by Bobek et al. in European population
where CTCs were detected with a higher rate in patients with
esophageal adenocarcinoma (n = 15/20) when compared with
patients with squamous cell carcinoma (75% vs 52%) [ 9 ]. This
study has also observed a significant increase in the detection of
CTCs in patients with adenocarcinoma with lymph node (N 2 or
N 3 ) and distant metastasis when compared to those patients with
esophageal squamous cell carcinoma. However, there was no1.3 Prognostic
Significance of CTCs
in Patients
with Esophageal
Adenocarcinomas
Vinod Gopalan and Alfred K. Lam