The flow chart here, you will notice that we completed quite
a bit. And before we move on, I want to show you
as to how much progress you have made. You walked through all the
different chemicals, radiation and viruses that are responsible for
carcinogenesis. You have talked about DNA repair and how if that
goes rye may result in carcinogenesis. Also talked about
inactivation of tumor suppressor gene, activation of oncogene. We
just completed our discussion of quickly how to evade apoptosis.
We talked quite a bit so does'nt this flow chart now seem a hack
of a lot more manageable. Where are we now? We are going to
increase the proliferation. We are going to progress the tumor
further. So therefore, just to make sure we're clear
understand the following. So you have proliferation taking place.
Proliferation takes place, hyperplasia. You are moving towards
cancer. What's the next step after hyperplasia that is a little bit
or a lot more dangerous. It's called dysplasia. And whenever you have
dysplasia if you pathologically, the term in which we will talk
about alot, not to worry. That nucleus that is oh so very important
for proliferation. If you are worried about cancer, now that nucleus
is referred to as being atypical. Atypical nucleus in pathology
means that oh my goodness, I have a cell that is about,
it' on the brink of going on to cancer.
Now once cancer sets in, or malignancy sets in, can the membrane
still be intact? Yes it can. You call that in-situ.
In-situ is a malignancy in which the membrane is intact. Very simple
as far as you are concerned. Eventually what may happen?
Progression then you metastasis. Let's first talk about the
progression. First we will do adenoma-carcinoma sequence.
Understand the topic. We are moving from benign neoplasia into
malignant neoplasia and then finally we have staging an invasion
and rupture the membrane and metastasis. The prototype for this
will be colorectal cancer. Quickly, you should be thinking about APC
on chromosome 5. If this then gets mutated then yout APC can no
longer control whom? Beta catenin. You have increase activity
of what biochemical process? Transcription, good. And you have
increased proliferation. Is that the only mutation? Not necessarily.
The mucosa is at risk, keep going. Then, this adenoma which has been
formed which means what? Increased proliferation. Other mutations
can also exist including K-RAS. Others also mutated include p53.
Also know SMAD, or SMAD-2. Finally, if there is increased
multifactorial type of mutations, at some point maybe telomerase
activity is enhanced. What's telomerase activity?
Oh my goodness, the tumor cell has found fountain of youth. Something
that Johnny Depp was looking for in Pirates of The Caribbean
but was never able to find. But the cancer cells were actually
successful. What does telomerase mean to you? Fountain of youth.
No matter how much damage takes place in DNA the telomerase activity
is going to then keep the DNA intact. Hence read please.
Telomerase are found in most genes that are carcinoma. You also
notice now that this polyp, if it's a villous type.
Don't worry about what type right now. The point is, if there is
increased proliferation increased mutations, you are going
to have invasion through the submucosa, mucosa. You'll pass through
the membrane and then off to the races unfortunately.
And this spread could be either lymphatic which carcinoma love. And
then maybe perhaps hematogeneous through your portal vein.
Where are you headed? Liver. Carcinogenesis, escape from immunity.
Why would your cancer cell want to be killed by immune cell.
Loss of immune function. Just a couple of things here. The
immunosurveillence normally destroys neoplastic cells via
recognition of 'nonself' antigens. Both the humoral and the CMI will
play a role. And patients with immune system dysfunction,
often times have an increased risk for neoplasia. Keep that in mind.
We see that clinically quite a bit. Staging.
What you will be responsible from now until the end of the pathology
course will be just a simple staging that you are responsible for
where the prognosis might be pretty decent to begin with. And then
with a particular stage, your prognosis drops like crazy.
For example, renal cell carcinoma. With renal cell carcinoma between
stages let's say, 2 and 3 you might then invade through the capsule.
Once you invade through the capsule, in renal cell carcinoma, you
have entered the renal vein. Metastasis. Towards where?
Well, towards the inferior vena cava. Are we clear? The staging
mechanism is called T, Tumor; N, number of lymph nodes;
M, will be metastasis. I'll keep coming back to this.