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Intracellular TCR-signaling pathway: novel markers for lymphoma diagnosis and potential therapeutic targets.
[hodgkin lymphoma, classical]
Despite
the
immunologic
functions
of
T
-
cell
receptor
signaling
molecules
being
extensively
investigated
,
their
potential
as
immunohistochemical
markers
has
been
poorly
explored
.
With
this
background
,
we
evaluated
the
expression
of
5
intracellular
proteins-
GADS
,
DOK
2
,
SKAP
55
,
ITK
,
and
PKC
α-involved
in
T
-
cell
receptor
signaling
in
normal
and
neoplastic
hematologic
tissue
samples
,
using
antibodies
raised
against
fixation-resistant
epitopes
of
the
5
molecules
.
All
5
antibodies
were
associated
with
normal
T
-
cell
differentiation
.
GADS
,
DOK
2
,
SKAP
55
,
and
ITK
turned
out
to
be
T
-
cell
lineage-
specific
markers
in
the
setting
of
lymphoid
and
myeloid
precursor
neoplasms
but
showed
differential
expression
in
peripheral
T-
cell
lymphoma
(
PTCL
)
subtypes
,
being
detected
in
PTCL
/
not
otherwise
specified
(
NOS
)
and
angioimmunoblastic
T-
cell
lymphoma
but
negative
in
anaplastic
large
cell
lymphoma
(
ALCL
)
.
Peripheral
B-
cell
lymphomas
were
consistently
negative
for
ITK
,
with
occasional
cases
showing
expression
of
DOK
2
and
SKAP
55
,
and
a
proportion
(
47
%
)
of
hairy
cell
leukemias
were
GADS
.
Notably
,
PKC
α
highlighted
a
defective
antigen
in
both
PTCL
/
NOS
(
6
%
)
and
angioimmunoblastic
T-
cell
lymphoma
(
10
%
)
,
mostly
negative
in
ALCL
,
and
was
aberrantly
expressed
in
classical
Hodgkin
lymphoma
(
65
%
)
,
Burkitt
lymphoma
(
48
%
)
,
and
plasma
cell
myeloma
(
48
%
)
.
In
conclusion
,
all
five
molecules
evaluated
play
a
role
in
T
-
cell
differentiation
in
normal
and
neoplastic
tissues
.
They
can
be
applied
confidently
to
routine
sections
contributing
primarily
to
assignment
of
T
-
lineage
differentiation
in
the
setting
of
hematopoietic
precursor
neoplasms
(
GADS
/
DOK
2
/
SKAP
55
/
ITK
)
and
for
the
differential
diagnosis
between
ALCL
and
PTCL
/
NOS
(
GADS
/
DOK
2
/
SKAP
55
/
ITK
)
or
classical
Hodgkin
lymphoma
(
PKC
α
)
.
Finally
,
association
with
specific
tumor
subtypes
may
have
therapeutic
potential
.
Diseases
Validation
Diseases presenting
"using antibodies raised against fixation-resistant epitopes of the 5 molecules"
symptom
hodgkin lymphoma, classical
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