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Aberrant TP53 detected by combining immunohistochemistry and DNA-FISH improves Barrett's esophagus progression prediction: A prospective follow-up study.
[esophageal adenocarcinoma]
Barrett
's
esophagus
(
BE
)
goes
through
a
sequence
of
low
grade
dysplasia
(
LGD
)
and
high
grade
dysplasia
(
HGD
)
to
esophageal
adenocarcinoma
(
EAC
)
.
The
current
gold
standard
for
BE
outcome
prediction
,
histopathological
staging
,
can
be
unreliable
.
TP
53
abnormalities
may
serve
as
prognostic
biomarkers
.
TP
53
protein
accumulation
detected
by
immunohistochemistry
(
IHC
)
indirectly
assesses
TP
53
mutations
.
DNA
fluorescent
in
situ
hybridization
(
FISH
)
on
brush
cytology
specimens
directly
evaluates
gene
locus
loss
.
We
evaluated
if
IHC
and
FISH
are
complementary
tools
to
assess
TP
53
abnormalities
and
tested
their
prognostic
value
in
a
long
-term
prospective
follow-up
of
a
BE
cohort
.
TP
53
IHC
on
tissue
sections
and
FISH
on
brush
cytology
specimens
were
evaluated
for
116
BE
patients
with
respect
to
the
different
histological
stages
.
The
TP
53
abnormalities
were
further
studied
in
a
panel
of
cell
lines
representative
of
the
Barrett
's
carcinogenic
sequence
.
For
91
patients
,
the
predictive
value
of
TP
53
abnormalities
with
respect
to
progression
to
HGD
/
EAC
was
tested
after
long
term
follow-up
.
The
frequency
of
IHC
and
FISH
TP
53
abnormalities
increased
significantly
with
increasing
histological
stage
(
P
 
<
 
0
.
001
,
Chi
(
2
)
-
test
)
.
Combining
the
techniques
detected
TP
53
abnormalities
in
100
%
of
patients
with
LGD
,
HGD
,
and
EAC
.
Multivariate
analysis
showed
that
IHC
(
hazard
ratio
:
17
,
95
%
CI
:
3
.
2
-
96
,
P
 
=
 
0
.
001
)
and
FISH
(
hazard
ratio
:
7
.
3
,
95
%
CI
:
1
.
3
-
41
,
P
 
=
 
0
.
02
)
were
both
independent
significant
predictors
of
progression
.
Combining
FISH
and
IHC
in
assessing
TP
53
abnormalities
leads
to
an
increased
detection
rate
of
TP
53
aberrations
and
improved
accuracy
for
predicting
BE
progression
.
©
2014
Wiley
Periodicals
,
Inc
.
Diseases
Validation
Diseases presenting
"long term"
symptom
adrenomyeloneuropathy
allergic bronchopulmonary aspergillosis
canavan disease
child syndrome
congenital diaphragmatic hernia
congenital toxoplasmosis
erythropoietic protoporphyria
esophageal adenocarcinoma
esophageal carcinoma
fabry disease
hirschsprung disease
hydrocephalus with stenosis of the aqueduct of sylvius
kindler syndrome
megacystis-microcolon-intestinal hypoperistalsis syndrome
oculocutaneous albinism
oligodontia
werner syndrome
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