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Computational analysis of p63(+) nuclei distribution pattern by graph theoretic approach in an oral pre-cancer (sub-mucous fibrosis).
[oral submucous fibrosis]
Oral
submucous
fibrosis
(
OSF
)
is
a
pre-cancerous
condition
with
features
of
chronic
,
inflammatory
and
progressive
sub-epithelial
fibrotic
disorder
of
the
buccal
mucosa
.
In
this
study
,
malignant
potentiality
of
OSF
has
been
assessed
by
quantification
of
immunohistochemical
expression
of
epithelial
prime
regulator
-
p
63
molecule
in
correlation
to
its
malignant
(
oral
squamous
cell
carcinoma
[
OSCC
]
and
normal
counterpart
[
normal
oral
mucosa
[
NOM
]
)
.
Attributes
of
spatial
extent
and
distribution
of
p
63
(
+
)
expression
in
the
epithelium
have
been
investigated
.
Further
,
a
correlated
assessment
of
histopathological
attributes
inferred
from
H
&
E
staining
and
their
mathematical
counterparts
(
molecular
pathology
of
p
63
)
have
been
proposed
.
The
suggested
analytical
framework
envisaged
standardization
of
the
immunohistochemistry
evaluation
procedure
for
the
molecular
marker
,
using
computer-aided
image
analysis
,
toward
enhancing
its
prognostic
value
.
In
histopathologically
confirmed
OSF
,
OSCC
and
NOM
tissue
sections
,
p
63
(
+
)
nuclei
were
localized
and
segmented
by
identifying
regional
maxima
in
plateau-like
intensity
spatial
profiles
of
nuclei
.
The
clustered
nuclei
were
localized
and
segmented
by
identifying
concave
points
in
the
morphometry
and
by
marker-controlled
watersheds
.
Voronoi
tessellations
were
constructed
around
nuclei
centroids
and
mean
values
of
spatial-relation
metrics
such
as
tessellation
area
,
tessellation
perimeter
,
roundness
factor
and
disorder
of
the
area
were
extracted
.
Morphology
and
extent
of
expression
are
characterized
by
area
,
diameter
,
perimeter
,
compactness
,
eccentricity
and
density
,
fraction
of
p
63
(
+
)
expression
and
expression
distance
of
p
63
(
+
)
nuclei
.
Correlative
framework
between
histopathological
features
characterizing
malignant
potentiality
and
their
quantitative
p
63
counterparts
was
developed
.
Statistical
analyses
of
mathematical
trends
were
evaluated
between
different
biologically
relevant
combinations
:
(
i
)
NOM
to
oral
submucous
fibrosis
without
dysplasia
(
OSFWT
)
(
ii
)
NOM
to
oral
submucous
fibrosis
with
dysplasia
(
OSFWD
)
(
iii
)
OSFWT-OSFWD
(
iv
)
OSFWD-OSCC
.
Significant
histopathogical
correlates
and
their
corroborative
mathematical
features
,
inferred
from
p
63
staining
,
were
also
investigated
into
.
Quantitative
assessment
and
correlative
analysis
identified
mathematical
features
related
to
hyperplasia
,
cellular
stratification
,
differentiation
and
maturation
,
shape
and
size
,
nuclear
crowding
and
nucleocytoplasmic
ratio
.
It
is
envisaged
that
this
approach
for
analyzing
the
p
63
expression
and
its
distribution
pattern
may
help
to
establish
it
as
a
quantitative
bio-marker
to
predict
the
malignant
potentiality
and
progression
.
The
proposed
work
would
be
a
value
addition
to
the
gold
standard
by
incorporating
an
observer-independent
framework
for
the
associated
molecular
pathology
.
Diseases
Validation
Diseases presenting
"squamous cell carcinoma"
symptom
carcinoma of the gallbladder
child syndrome
dystrophic epidermolysis bullosa
epidermolysis bullosa simplex
esophageal adenocarcinoma
esophageal carcinoma
esophageal squamous cell carcinoma
junctional epidermolysis bullosa
kallmann syndrome
kindler syndrome
liposarcoma
monosomy 21
oculocutaneous albinism
oral submucous fibrosis
papillon-lefèvre syndrome
This symptom has already been validated