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The value of thioredoxin family proteins and proliferation markers in dysplastic and malignant gallbladders in patients with primary sclerosing cholangitis.
[carcinoma of the gallbladder]
Patients
with
primary
sclerosing
cholangitis
(
PSC
)
have
an
increased
risk
for
biliary
and
gallbladder
malignancy
and
markers
of
early
malignancy
in
PSC
are
lacking
.
The
aims
were
to
evaluate
biomarkers
to
look
for
premalignancy
/
malignancy
.
All
available
gallbladder
specimens
(
n
Â
=
Â
53
)
in
patients
with
PSC
at
Karolinska
University
Hospital
between
1985
and
2006
were
reviewed
.
Immunohistochemical
staining
for
p
53
,
Ki-
67
,
Cyclin
D
1
and
the
thioredoxin
family
redox
proteins
;
Thioredoxin
reductase
1
(
TrxR
1
)
,
isoform-
TrxR
1
-
v
.
2
.
3
.
5
,
Thioredoxin
(
Trx
1
)
and
Glutaredoxin
1
(
Grx
1
)
was
performed
on
tissues
from
patients
with
carcinoma
(
n
Â
=
Â
6
)
,
dysplasia
(
n
Â
=
Â
7
)
and
non-cancerous
gallbladder
epithelium
(
n
Â
=
Â
6
)
.
Dysplasia
and
carcinoma
were
found
in
16
/
53
(
30
%
)
cases
.
Inflammation
and
fibrosis
of
the
gallbladder
wall
were
more
common
in
tissue
with
gallbladder
dysplasia
/
carcinoma
than
in
benign
tissue
12
/
25
(
48
%
)
versus
4
/
28
(
12
%
)
(
p
Â
<
Â
0
.
01
)
and
in
13
/
21
(
62
%
)
versus
3
/
32
(
9
%
)
(
p
Â
<
Â
0
.
0001
)
,
respectively
.
Immunoreactivity
for
p
53
,
Ki
67
,
Cyclin
D
1
was
detected
in
significantly
more
cases
of
dysplasia
/
carcinoma
of
the
gallbladder
than
in
non-cancerous
epithelium
.
2
/
19
(
11
%
)
of
the
samples
were
positive
in
non-cancerous
epithelium
versus
7
/
17
(
41
%
)
in
dysplasia
/
carcinoma
(
p
Â
<
Â
0
.
05
)
for
TrxR
1
-
v
.
2
.
3
.
5
.
Grx
1
was
down
regulated
;
more
specifically
15
/
19
(
79
%
)
positive
cases
in
non-cancerous
epithelium
versus
7
/
17
(
41
%
)
in
dysplasia
/
carcinoma
.
PSC
patients
have
a
frequency
of
gallbladder
dysplasia
/
carcinoma
of
30
%
in
operative
specimens
.
The
overexpression
of
TrxR
1
-
v
2
,
3
,
5
and
down
regulation
of
Grx
1
in
dysplastic
gallbladder
epithelium
suggest
that
these
proteins
should
be
further
evaluated
as
possible
future
immunohistochemical
markers
in
the
early
diagnosis
of
biliary
malignancy
in
PSC
.
Diseases
Validation
Diseases presenting
"gallbladder malignancy"
symptom
carcinoma of the gallbladder
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