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of samples. In 2006, Langer and colleagues assessed the expression
of HER2, p53, p16, p27, cyclin D1, and epidermal growth factor
receptor (EGFR) in a series of 137 primarily resected esophageal
adenocarcinoma samples by tissue microarray. They concluded that
these proteins are involved in the pathogenesis of esophageal ade-
nocarcinomas [ 2 ]. In 2007, Kuester and colleagues explored the
promoter hypermethylation and protein expression of proapoptotic
death-associated protein kinase (DAPK) through the multistep cas-
cade of Barrett esophagus. They considered DAPK inactivation by
promoter hypermethylation as an early event in carcinogenesis of
Barret esophagus and suggest that a reduced protein expression of
DAPK likely plays a role in the development and progression to
esophageal adenocarcinoma [ 3 ]. Also in the same year, Wang and
colleagues studied tumor specimens from 103 patients with surgi-
cally resected esophageal and esophagogastric junction adenocarci-
nomas. They noted that EGFR expression in these carcinomas
correlated with poor prognostic factors and could be used to pre-
dict patient outcomes. In 2008, Boult and colleagues reported that
progression to adenocarcinoma is associated with enhanced expres-
sion of iron carry proteins. These events caused an increased intra-
cellular iron and cellular proliferation suggesting that they represent
a novel mechanism of esophageal carcinogenesis [ 4 ].
In 2012, Prins and colleagues evaluated the expression of
m-TOR (mammalian target of rapamycin) from 154 patients with
esophageal adenocarcinoma, with TMA by immunohistochemical
staining. m-TOR overexpression was detected in 19.7% of patients
with esophageal adenocarcinoma and was associated with poor
overall survival of patients [ 5 ]. In the same year, Dibb and col-
leagues by using tissue microarrays and metadata analysis of micro-
array data found that FOXM1 and its target gene PLK1 overexpressed
in esophageal adenocarcinomas [ 6 ]. In 2013, Storr and colleagues
studied the expression of calpain-1, calpain-2, and calpastatin in
esophageal adenocarcinoma in 88 patients who received neoadju-
vant chemotherapy and 140 patients who received surgery alone by
immunohistochemistry using TMA. Calpain-1, calpain-2, and cal-
pastatin expression were associated with adverse cancer-specific sur-
vival in the patients having neoadjuvant therapy [ 7 ].
In 2015, Prins and colleagues studied on 154 patients with
esophageal adenocarcinoma by TMA to identify epithelial to mes-
enchymal transition (EMT) by analyzing the immunohistochemi-
cal staining intensity of E-cadherin, ß-catenin, epidermal growth
factor receptor (EGFR), neuronal cadherin (N-cadherin), and
Cyclin D. This study supports the presence of EMT in esophageal
adenocarcinoma. Moreover, EGFR overexpression was indepen-
dently associated with poor survival of patients with esophageal
adenocarcinoma [ 8 ]. In 2017, Stein et al. analyzed 111 resected
esophageal adenocarcinoma using TMA. Inflammation was
assessed by histological examination as well as identifying theNassim Saremi and Alfred K. Lam