00:01
Histology is not the only way
that we evaluate brain tumors.
00:04
Historically, histologic grading
was the primary method
for diagnosing tumors.
00:09
And in the last 10 to 15 years,
we've learned that
molecular assessments,
looking at the tumors genes,
gives us an important
window into how tumors do,
how patients will do,
and how we should treat
these tumors?
I don't need you to understand all
the details of this slide,
but what we see here
is that low-grade gliomas,
things can go very differently
depending on the type of
low-grade glioma that it is,
and the type of genes
that we see in that tumor.
00:37
Here on the left side, we're looking
at a Kaplan-Meier survival curve.
00:42
At the time zero point,
the zero point of the X axis
100% of patients are alive.
00:48
And as we move forward in the graph,
we see that patients succumb
to their glioma and die.
00:54
We see that some patients
do really well.
00:56
These IDH and TERT
mutated tumors,
a lot of patients are alive
for a long time.
01:02
The same is true for
triple positive tumors,
not quite as much for IDH only,
IDH mutant only tumors,
not quite as much
for the triple negative tumors,
and not near as much
for these TERT only tumors.
01:15
I don't need you to know all the
details of the molecular features,
except that genetic testing
is important
for determining
how tumors will act,
how aggressive they will be,
how patients will do
and what treatment we select?
For high grade tumors,
tumors that look like a glioblastoma
under the microscope,
molecular testing
is also important,
but it's not quite as helpful,
as you see
as for the low grade gliomas
where the vast majority of patients,
regardless of their
molecular signature,
will have a very aggressive course,
regardless of the genetic events.
01:50
So we can put that all together
and when we're evaluating
a brain tumor,
we start with the
histologic appearance.
01:56
What did this tumor look like
under the microscope?
Did it look like an
oligodendroglioma?
A mixed oligoastrocytoma,
which is a diagnosis
that's falling out of favor?
An astrocytoma
or a glioblastoma?
And we'll start our assessment
of the tumor their.
02:13
Tumors that are
histologically appear as an
oligodendroglioma, or astrocytoma
are termed diffuse gliomas.
02:19
And we start looking at
key molecular events,
genetic changes in the tumors,
that will tell us,
how that tumor will evolve
and how that patient may do?
The first gene we look at
is something called IDH
or Isocitrate dehydrogenase.
02:33
And it can either be
mutant or wild type.
02:36
IDH mutant gliomas tend to respond
better to treatment.
02:40
They tend to not grow as quickly.
Patients tend to do better.
02:43
So we want to know
about those.
02:45
IDH wild type tumors are
less responsive to treatment.
02:48
And those patients sometimes
the course can look
very similar to a
grade IV glioblastoma.
02:55
We can further subdivide
these tumors
based on other
molecular events.
02:59
The IDH mutant tumors,
those favorable risks
likely to respond
to treatment tumors,
can acquire a loss
of the 1 p arm.
03:07
the p arm of chromosome 1,
or the q arm of chromosome2,
which we call 1p19q codeletion,
loss of both of those areas
of the chromosome.
03:17
And those are
oligodendrogliomas.
03:18
And they do exceptionally well
with treatment
and patients tend to do well
with those tumors.
03:23
In contrast, IDH mutant tumors can
acquire a mutation in the TP53 gene.
03:29
This is the most common gene
to be mutated in all of cancer,
and can be seen in gliomas.
03:34
And those tumors tend to take on
the appearance of an astrocytoma
and have an intermediate prognosis.
03:41
We said IDH wild type tumors
can often be quite aggressive
and not respond to treatment.
03:46
And are termed
IDH wild type diffuse gliomas,
and sometimes can act
a very aggressive
just like the grade IV glioblastoma.
03:54
Similarly, grade IV glioblastomas
can be subdivided by their genes.
03:59
By that IDH gene
as either
IDH mutant gliomas or
IDH wild type glioblastomas.
04:04
So you can see
how our pathologist,
and our tumor surgeons,
and neurologist,
start with the histology,
add in the genetics,
and come up
with a final diagnosis
of one of these
five major types of gliomas.