Introduction
:
-
The majority of cancers are
diagnosed
using
excised biopsy specimens.
These are graded, using a g
old
-
standard
histopathology
protocol
based
on
haemotoxylin and eosin (
“H+E”
)
chemical
staining
. However
the grading is done by eye
and i
f the same biopsy is graded by
different
practitioners, they typic
ally only agree ~70%
of the time.
The
resulting
overtreatment
problem
constitutes
a
massive
unmet
need
worldwide.
Objective:
-
Our
new
‘Digistain
’
technology,
uses mid
-
infrared imaging to map
the
fractional concentration of nucleic acids, i.e.
the n
uclea
r
-
to
-
cytoplasmic chemical ratio
(NCR) across an unstained biopsy section. It
allows a quantitative “Digistain index” (DI)
score, corresponding to the NCR, to be
reproducibly extracted from an objective
p
hysical measurement of a cancer. O
ur
objective
here
i
s to evaluate
its
potential
for
aiding cancer diagnosis for the first time. We
correlate the DI scores with H+E grades in a
double
-
blind clinical pilot trial.
Methods:
-
T
wo adjacent slices were taken
from
75
breast cancer FFPE blocks; one was
graded with the standard H+E protocol, and
also used to define a “Region of Int
erest”
(RoI). Digistain was then used to acquire a DI
value averaged over the corresponding RoI
on the other
(unstained)
slice
and the
r
esults
were
statistically analysed.
Results
:
-
We find the DI score correlates
significantly (p=0.0007) with
tumor
grade
in
a way that promises to significantly reduce
the inherent subjectivity and variability in
biopsy grading.
Discussion: The NCR is elevated by increased
mitotic activity because
cells
divide when
they are younger
and
, on average, become
smaller as
the di
sease progresses. Also, extra
DNA and RNA is generated as the
nuclear
transcription
machinery goes awry and
nuclear pleomorphism
occurs
. Both effects
make the NCR a
recognized
biomarker for a
wide range of
tumors,
so
we expect Digistain
will
find application in a
very
wide range of
cancers.