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Diagnostic utility of p16, CDK4, and MDM2 as an immunohistochemical panel in distinguishing well-differentiated and dedifferentiated liposarcomas from other adipocytic tumors.
[well-differentiated liposarcoma]
Adipocytic
tumors
are
the
most
common
type
of
soft
tissue
neoplasms
.
Distinguishing
atypical
lipomatous
tumor
-
well-differentiated
liposarcoma
(
WDL
)
from
benign
adipocytic
neoplasms
and
dedifferentiated
liposarcoma
(
DDL
)
from
pleomorphic
or
myxoid
liposarcoma
(
LPS
)
can
be
difficult
.
WDL
and
DDL
characteristically
harbor
amplifications
of
the
MDM
2
and
CDK
4
cell
cycle
oncogenes
with
protein
overexpression
and
can
also
overexpress
the
cell
cycle
regulator
p
16
.
We
assessed
the
utility
of
immunohistochemistry
for
CDK
4
,
MDM
2
,
and
p
16
in
the
routine
histopathologic
diagnosis
of
WDL
/
DDL
from
other
adipocytic
tumors
.
Immunohistochemistry
for
the
trio
of
markers
was
performed
on
216
adipocytic
neoplasms
(
31
WDLs
,
57
DDLs
,
11
myxoid
LPS
,
2
pleomorphic
LPS
,
91
lipomas
(
including
intramuscular
,
fibro
,
angio
,
and
ossifying
subtypes
)
,
18
spindle
/
pleomorphic
lipomas
,
and
6
hibernomas
.
Sixty
-
eight
percent
of
WDLs
and
72
%
of
DDLs
expressed
all
3
antigens
,
whereas
100
%
of
WDLs
and
93
%
of
DDLs
expressed
at
least
2
antigens
.
The
sensitivity
and
specificity
of
the
trio
for
detecting
WDLs
/
DDLs
were
71
%
and
98
%
,
respectively
.
The
sensitivity
and
specificity
of
CDK
4
for
detecting
WDLs
/
DDLs
were
86
%
and
89
%
,
those
of
MDM
2
were
86
%
and
74
%
,
and
those
of
p
16
were
93
%
and
92
%
,
respectively
.
The
immunohistochemical
trio
of
CDK
4
,
MDM
2
,
and
p
16
is
a
useful
ancillary
diagnostic
tool
that
provides
strong
support
in
distinguishing
WDLs
and
DDLs
from
other
adipocytic
neoplasms
and
is
potentially
more
sensitive
than
previously
assessed
combinations
of
CDK
4
and
MDM
2
.
p
16
was
the
most
sensitive
and
specific
marker
for
detecting
WDL
/
DDL
,
and
the
combination
of
CDK
4
and
p
16
is
of
more
discriminatory
value
than
the
combination
of
either
with
MDM
2
,
the
least
sensitive
and
specific
of
the
3
markers
.
Diseases
Validation
Diseases presenting
"lipomatous tumor"
symptom
dedifferentiated liposarcoma
liposarcoma
pleomorphic liposarcoma
well-differentiated liposarcoma
This symptom has already been validated