FISH (Fluorescent in situ hybridization)

FISH stands for Fluorescent in situ hybridzation. It is a procedure - not a test in that you can test for a wide variety of genetic conditions using this technique.
Suppose you know that a gene that you know is responsible for a specific disease. This is one gene among 50,000 so finding this one gene in a cell could be difficult. BUT, supposing you had a compound which - when it binds to that one gene - will fluoresce and be picked up by photo sensitive instruments.
So - there are lots of tests out there that use FISH technology.It is just that you might not know which tests since most tests will not be identified as such since it is a technique.
 

Gayle, At the present time, there are quite few opinions about the use of molecular testing for CLL. One side holds that all forms of cutting edge test must be done while an opposing side says that there is not enough evidence that the answers are meaningful and that you get all the information you need/want through a careful examination of patient progress. Of course, there are also people in between who get the information if they fell there is reason to do so (infections, unusual symptoms, etc.) and there are people who will get the information just in case some years down the line it might be useful.
The biggest problem with all DNA - based testing right now is that it is so new it is hard to determine if it is meaningful or not. For example - it is statistically meaningful to have a blood glucose change from an 80 to a 94 but it is clinically irrelevant in that both values are perfectly adequate numbers. It may be clinically significant that someone has a gene for some abnormal hemoglobin but if it happens that this hemoglobin works ok, then for the individual,it is a useless bit of information in reality.
Sorry I can't really answer your question but we won't have that answer for a few years. I guess the best answer is that you need the results that make you comfortable.
 

13 deletion is the best possible news in CLL. First described as a problem in CLL by David Oscier in Bournemouth the missing region has been narrowed to a small area at 13q14. There are a maximum of 5 genes in this area, but none has been shown to be implicated in CLL. It is a strange phenomenon where losing a gene makes the prognosis better, and no-one understands it. It has been known for nearly 20 years that patients who lack this bit of chromosome (and around 50% lack it) have the best outlook.

Flow cytometry results (if that is what you are referring to) usually mean negative = less than 10% of the cells are visualized by the "stain" positive = more than 20% of the cells are visualized by the "stain" I've put stain in quotation marks because it is really a combination of monoclonal antibodies directed against a specific antigen marker on the cell and some type of fluorescent compound. When the antibody/fluorochrome is bound to the cell, the fluorochrome emits energy that is picked up by light sensitive photomultiplier tubes and reported as a positive. Many systems are closed in that the operator never sees the energy burst or, since different fluorochrome do indeed give off different colors, any color change so the v visualization is entirely performed by the instrument.

FISH (fluorescent in situ hybridization ) is really a technique, not a specific test. An antibody is bound onto a fluorescent dye and this combination is mixed with a population of cells. Cells with the antigen which can bind to the antibody can fluoresce while cells that do not have the antigen will not. It is as good as the quality of the antibody which, the case of CLL is very good. Most of the time, FISH testing is performed on a sample of blood or bone marrow "as it comes out" which means that the cell numbers reflect the cell numbers in the body.

You can cause these cells to undergo mitosis and increase the number of cells but with stimulations comes the potential for mistakes and false positives.

ZAP 70 is a FISH technique test, that is, it uses the same techniques as say CD19 or CD20 so you would think that it should be as good but it has many many problems:

*It is labile - which means it can be destroyed while you are setting up the test. *It's an intracellular antigen. The reagent has to be able to get into the cell not just attach to something on the outside - which means that it might not do that well. *. It's extraordinarily dim so that even a good positive is hard to see. *. There's no gold-standard assay. No one knows for sure how to report it. * The antibodies aren't so wonderful.

The balancing act then is this test COULD give you some important information but until the technical difficulties are worked out, it will be sometime before it is considered highly usable.

When should you have a FISH test?

If you definitely need treatment a FISH test would pick up 17p abnormalities
and might make your doctor keen to explore less conventional treatments such
as CAMPATH, HDMP or allograft.

When you are first diagnosed a FISH test will help in giving a prognosis if
you want to know - some patients would rather not know about bad news.

In my opinion - and not every CLL doctor believes as I do - the best set of
prognostic tests are VH gene mutations, ZAP-70, CD38 and FISH.

Serum Thymidine Kinase is only available in Germany as far as I know, but it
looks to be a very good prognostic indicator. Beta-2 microglobulin performs
as well as CD38. LDH is too non-specific. Soluble CD23 is unavailable in most
labs and has not been evaluated against the others.

Stage is still important as is gender.

Some doctors believe that patients who fit the criteria of smoldering CLL
need not have any more tests but should wait and be watched and have the tests
if the disease progresses.

FISH is a quick an easy way of detecting chromosomal abnormalities. It
detects del 13q14, which has a good prognosis, trisomy 12 which has a slightly
worse than average prognosis, del 11q23 which has a worse than average prognosis
and del 17p13 which has the worst of all prognosis. Some labs also offer
del 6q, which seldom occurs alone and is a late change. If you have none of
these then you have a prognosis better than trisomy 12 but worse than del 13q14.

However other abnormalities are found in CLL. Translocations at 14q32 do
occur in CLL. Even t(14;18) which is normally found in follicular lymphoma can
be seen in CLL, and t(14;19), though very rare is characteristic of a
particularly nasty form of CLL. We have also seen trisomy 18 and trisomy 19. These
abnormalities are not picked up by FISH, you have to have full karyotyping.
Unfortunately, this is not available in most labs because it is quite difficult
and most labs have not been able to do it successfully. Even our lab, which
has the largest series of karyotypined CLLs in the world has largely given it
up, except in special cases because FISH is so mush quicker, cheaper and
easier.

The sort of case where we would do karyotyping is where the FISH result did
not fit with the clinical pattern

11q deletions are sometimes bad news, but not always. Survival curves are intemediate between trisomy 12 and 17p deletions. We think this is because both ATM genes need to be affected for an ill effect. Demethylation (inactivation) of the remaining ATM gene seems to occur in some patients and these have a poor prognosis, but if the other 11q gene is still working then things seem to be alright. trouble is, we do not have an easy test to tell whether this is the case.

FISH testing is pretty standard wherever it is done and will tell you about
abnormalities on chromosomes 11q, 12, 13q and 17p. These are the only
chromosomal abnormalities that matter in CLL. Karyotyping in CLL, where all the
chromosomes are looked at is so badly done that no results should be believed
(unless they are done in our lab or one in Germany - I jest, but you get my
meaning). FISH does not tell you about IgVH mutations. There are several labs
that do this but people are abandoning the test for ZAP-70 which is quicker and
cheaper to do. Unfortunately ZAP-70 as it is done in commercial laboratories
is not reliable. Preliminary results in Europe show the test to give 20% false
negatives.