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Prognostic significance of Kit receptor tyrosine kinase dysregulations in feline cutaneous mast cell tumors.
[cutaneous mastocytosis]
Feline
cutaneous
mast
cell
tumors
(
FeCMCTs
)
are
characterized
by
variable
biological
behavior
.
Development
of
multiple
nodules
and
potential
visceral
involvement
,
along
with
inconsistency
of
conventional
prognostic
aids
,
justify
uncertainty
in
differentiating
benign
from
malignant
forms
.
c-
Kit
proto-oncogene
activating
mutations
have
been
reported
in
feline
mast
cell
tumors
(
MCTs
)
,
but
their
prognostic
relevance
was
not
investigated
.
This
study
was
performed
on
FeCMCTs
with
variable
clinical
outcome
to
assess
whether
Kit
cytoplasmic
immunohistochemical
labeling
can
be
regarded
as
indicative
of
c-
Kit
mutations
and
to
evaluate
the
relationship
between
Kit
dysregulation
and
survival
.
Twenty
-
four
cats
diagnosed
with
a
primary
cutaneous
MCT
were
enrolled
.
Kit
immunohistochemical
pattern
and
c-
Kit
(
exons
8
,
9
,
11
)
mutational
status
were
assessed
in
34
tumor
samples
.
Risk
factors
affecting
survival
were
a
number
of
mitoses
greater
than
5
per
10
HPFs
(
P
=
.
017
)
and
cytoplasmic
Kit
labeling
(
P
=
.
045
)
.
Increased
mitotic
activity
was
associated
with
Kit
cytoplasmic
expression
(
P
=
.
01
)
.
c-
Kit
encoding
mutations
were
present
in
19
(
56
%
)
tumors
(
exon
8
,
19
%
;
exon
9
,
71
%
;
exon
11
,
10
%
)
,
however
,
they
were
not
significantly
related
to
protein
expression
and
they
had
no
influence
on
prognosis
.
Additionally
,
in
6
of
9
(
67
%
)
cats
,
multiple
nodules
from
the
same
cat
had
different
mutational
statuses
.
Mutations
in
the
fifth
immunoglobulin-like
domain
of
Kit
occur
frequently
in
FeCMCT
,
but
they
are
variably
associated
with
aberrant
protein
expression
and
do
not
appear
to
be
strictly
correlated
with
biological
behavior
.
These
findings
need
to
be
confirmed
in
larger
series
,
and
exploration
of
further
genomic
regions
of
c-
Kit
is
warranted
.
Diseases
Validation
Diseases presenting
"to evaluate the relationship between kit dysregulation and survival"
symptom
cutaneous mastocytosis
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