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Vitamin D receptor is highly expressed in precancerous lesions and esophageal adenocarcinoma with significant sex difference.
[esophageal adenocarcinoma]
Bile
acid
reflux
into
the
esophagus
is
important
in
the
development
of
esophageal
adenocarcinoma
(
EAC
)
.
Recently
,
vitamin
D
receptor
(
VDR
)
was
recognized
as
a
bile
acid
receptor
as
well
as
a
vitamin
receptor
.
Expression
of
VDR
is
reported
to
influence
the
development
of
various
types
of
cancer
,
such
as
those
of
the
breast
,
liver
,
and
colon
.
However
,
little
is
known
about
the
role
of
VDR
in
esophageal
neoplasms
.
We
investigated
the
clinicopathological
role
of
VDR
in
esophageal
tumors
.
We
analyzed
genomic
DNA
from
116
EACs
for
copy
number
aberrations
.
The
VDR
locus
was
amplified
in
7
%
of
EACs
.
Expression
of
the
VDR
protein
was
also
detected
by
immunohistochemistry
from
tissue
microarrays
created
from
tissues
of
Barrett
esophagus
(
BE
)
,
low
-grade
(
LGD
)
and
high
-grade
dysplasia
(
HGD
)
,
columnar
cell
metaplasia
(
CCM
)
,
squamous
epithelium
(
SE
)
,
EAC
,
and
esophageal
squamous
cell
carcinoma
(
ESCC
)
.
The
protein
was
highly
expressed
in
88
%
of
CCM
(
58
/
66
)
,
95
%
of
BE
(
35
/
37
)
,
100
%
of
the
19
LGD
,
94
%
of
HGD
(
15
/
16
)
,
and
79
%
of
EAC
(
86
/
109
)
,
but
expression
in
SE
and
ESCC
was
rare
.
Female
patients
with
EAC
and
CCM
were
significantly
less
likely
to
have
high
VDR
expression
than
male
patients
.
The
overall
survival
rate
was
significantly
different
for
patients
with
tumors
exhibiting
VDR
amplification
versus
nonamplification
.
Our
findings
suggest
that
VDR
plays
a
role
in
the
early
development
of
EAC
through
a
bile
acid
ligand
.
The
sex
difference
in
VDR
expression
may
help
to
explain
why
men
have
a
high
incidence
of
EAC
.
Diseases
Validation
Diseases presenting
"barrett esophagus"
symptom
esophageal adenocarcinoma
This symptom has already been validated