Myelodysplastic Syndrome Diagnosis

Many cancers grow when there’s a glitch in the DNA of our cells. Sometimes that error is passed down from a parent to their child, and sometimes it’s caused by external factors like tobacco use. No matter the origin, understanding the genetic makeup of a cancer cell can help define a cancer diagnosis and ultimately lead to better care for a patient.

Commonly called FISH, fluorescence in situ hybridization is a laboratory-based test that helps build out the full picture of a cancer diagnosis by zooming in on the genetic material in the cell – known as chromosomes. FISH is most commonly used in breast cancer, sarcoma, lymphoma, multiple myeloma, myelodysplastic syndrome (MDS) and some leukemias.

Pathologist Sanam Loghavi, M.D., shares how FISH testing works and the multiple uses of this cytogenetic technique.

What is fluorescence in situ hybridization?

To understand fluorescence in situ hybridization (FISH), it’s important to review the basics of how our cells work. At the center of each cell is a nucleus. There, you will find 23 pairs of chromosomes (a total of 46) that hold the instructions for a cell’s growth, survival and reproduction. These instructions are contained in our DNA.

We grow new cells when a single cell divides into two daughter cells. It first copies its genetic material so that it can pass along those 46 chromosomes to each daughter cell. It’s a very regulated process.

But cancer cells don’t follow the rules. The number of chromosomes or their structural makeup often varies. FISH helps us to see the number of chromosomes and their structure within a cell and detect errors.

How does fluorescence in situ hybridization work?

We look at cells that are gathered during the diagnostic work-up. For blood cancers, we test samples taken during a blood draw or with a bone marrow aspiration. For solid tumors, we work with tissue from the biopsy that is preserved in wax.

We use segments of artificial DNA that have fluorescent molecules attached called probes. They’re engineered in the lab to target specific areas of chromosomes.

Taking the patient’s cells and the probe, we hybridize them. That means a strand from the probe binds to the complementary DNA strand from the patient’s sample. As it binds, it glows to signal an abnormality in the chromosomes the probe is created to examine. For example, if normally you have a copy of a gene in the long arm of chromosome one and there are extra copies of that region, then we’re going to see more glowing signals than we would with a normal cell.

What does a FISH test show?

With a FISH test, we’re looking at the number of chromosomes or their structural makeup within a cancer cell. There are a few genetic mistakes that can occur:

• Duplication/amplification – We find extra copies of chromosomes, parts of chromosomes or genes.
• Deletion – There are chromosomes or parts of the chromosome missing.
• Translocation – A portion of one chromosome detaches and reattaches to another chromosome. This occurs when, for example, a part of chromosome 9 attaches to chromosome 22 and a part of chromosome 22 attaches to chromosome 9, it’s referred to as the Philadelphia chromosome rearrangement. It’s found in some patients with acute lymphoblastic leukemia (ALL).

How are the results of fluorescence in situ hybridization used in cancer care?

There are four ways the results are used in cancer care:

• For diagnosis – Some chromosomal errors have been tracked in many patients and now define a specific cancer diagnosis. For example, a subtype of acute myeloid leukemia called acute promyelocytic leukemia is defined by the translocation between the chromosomes 15 and 17.
• For prognosis – How quickly a cancer grows and its ability to spread is determined in part by its genetics. Using FISH results, we can better predict how a tumor will behave. For example, if a patient with myelodysplastic syndrome has a tumor that shows the loss of chromosome 7, it usually progresses quickly. On the other hand, another patient with MDS whose tumor shows the deletion of chromosome 20 typically sees the disease progress more slowly. But both patients have MDS.
• For predicting response to therapy – Using FISH, we can identify genetic changes that are linked to how well a tumor responds to certain therapies, so we can predict if a tumor will be sensitive or resistant to a certain drug. An example is when we identify extra copies of chromosome 17, which is known as HER2. When we see this, we know this tumor will likely be vulnerable to the drug trastuzumab (Herceptin).
  
• For surveillance – If treatment has been successful, a patient’s chromosomes should go back to normal, and we should see the expected 46 in each cell. But if abnormalities are found after treatment during another round of testing, it means that patient has residual disease and has a high risk of the cancer coming back.
  

What do you want patients with cancer to know about FISH testing?

FISH can reveal a lot about a tumor that can help make treatment more successful, but it’s not used with every type of cancer. It’s also not the only technique we have. If FISH isn’t part of your treatment plan, talk with your doctor to learn what other approaches are options for you. The more that’s known about your cancer, the more effective treatment can be.

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