| SUSAN LECLAIR |
To understand PCR results, you need to understand the actual procedure.
DNA is taken from cells and "encouraged" to replicate (make copies of
itself). Depending on the amount of time that it is given, you end end
up with either 1,000,000 to 1,000,000,000 copies of the DNA. This
increased number is then tested for the presence of a specific piece of
DNA.
So - 1. This is extraordinarily sensitive. As a consequence, you might
have only 1 cell in your entire body that is positive and it might show
up here.
2. The test does not discriminate between live cells, damaged cells, or
dead cells. So it is possible that the positive is a result of the dead
cell's DNA or the cell that cannot multiply because the rest of the cell
is so damaged or a cell to be concerned about.
3. As with all tests but especially highly sensitive ones, there is
always the possibility of false positives. Exactly how trusting are you
that your DNA can copy itself a billion times under stressed conditions
(shortened time) with absolute perfection? And even if a mistake happens
only once, it will result in a positive just as if the DNA was really
there.
4. In remissions, the first signs are seen in the blood stream, followed
by the bone marrow aspirate/biopsy, then by the cytospin in the fluids,
then by chromosomal analysis, then FISH and finally PCR. So the last
place to "become" negative will be the PCR . Commonly, the term
"complete remission" refers to the absence of the disease in the blood
and bone marrow. Chromosomal remission means nothing is found in the
karyotype (if that is a possible test for that disease) or FISH. Genetic
remission means that all tests, including the PCR, are negative.
|
| SUSAN LECLAIR |
|
Dear Joe,
I took your " I think Susan said something" as a clue to
restate the situation ;-)
The PCR
technique starts with DNA - not with live cells and then
every single strand of DNA is multiplied somewhere
between 10,000 and 1,000,000 times. This increases the
sensitivity of the test immensely. If the test is 90%
positive, then there is no doubt that it is a "true"
positive. But when you get down into the 1-5% positivity,
you have to question the possibility of a false
positivity. The false positives include
1. The
piece of DNA may come from a cell which is actually dead
and therefore will not be able to continue the disease
process. 2. The piece of DNA may come from a cell which
is still alive but so damaged that it will not be able
to continue the disease process. 3. The positive is due
to a mistake that actually occurred during the
multiplication part of the test procedure.
Most
folks now hedge their bets and call this "minimum
residual disease". |
|
|
| SUSAN LECLAIR |
Dennis, PCR does frequently oscillate between
positive and negative. Part of this reason is the extremely high
sensitivity of the procedure. It is so sensitive that even one almost
dead or dead cell can be picked up. Another reason is that, because of
the sensitivity, occasional false positive results are possible. And a
third part of this is that we still do not fully (or even marginally)
understand the concept of "minimum residual disease".
When you were first diagnosed, you probably had somewhere in the area of
100,000,000,000,000 malignant cells. We know what that is and we know
the outcome of that large a tumor burden. Remission occurs around
1,000,000 cells. PCR remission is around 10,000 cells. We do know that
most people have some malignant cells in them every day. If you have 1
cell, is that cancer? Not as we have always known it, it isn't. So what
do we say about a person who has 10 bad cells - so far we know that
their quality of life is excellent. - we know that they appear to be no
t at risk for anything troublesome - we know that all other functions
appear to be within reference range
We believe them to be cancer survivors - who just need to take care of
themselves. But we cannot predict the future.
|
| TERRY HAMBLIN
17 April 2005 |
Remission is a
term used in acute leukemia. It means that there is no detectable
disease in the body. 'Detectable' is a variable feast. It depends on how
good a detective you are. The standard way of looking is with a
microscope. If you can't see any leukemic cells then you are said to be
in complete remission. But leukemic cells cannot be separated from their
normal counterparts simply by looking down a microscope and there may be
1,000,000,000 leukemic cells left in the body. There are more sensitive
techniques such as PCR for looking fro 'minimal residual disease'. Even
they can miss very small numbers of cells (less than 100,000 leukemic
cells).
It is hard to
get your head round these numbers. In a teaspoonful of blood there are
25,000,000,000 red blood cells. Another way of looking at it is to
remember that we make 3 million new blood cells every second. Another
way is to remember that only 10% of the cells in your body are human.
The term
remission has therefore spread from acute leukemia to other conditions
including CLL. What it means is that we cannot detect any disease, but
we don't know whether we got it all. If we haven't then it will come
back, but only time will tell.
In the film
"Battle of Britain" Laurence Olivier (playing Field Marshall Lord
Dowding) is asked whether the number of 'kills' of German aircraft has
been exaggerated as the German High Command had claimed. Olivier replies
with disdain something like, "If we are right we will win; if they are
right we will lose." Time will tell. |
