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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
"common type"
symptom
alexander disease
cutaneous mastocytosis
dedifferentiated liposarcoma
dentin dysplasia
dentinogenesis imperfecta
erythropoietic protoporphyria
esophageal carcinoma
hereditary cerebral hemorrhage with amyloidosis
liposarcoma
oculocutaneous albinism
oligodontia
pendred syndrome
pleomorphic liposarcoma
pyomyositis
well-differentiated liposarcoma
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