FISH testing

When you have cancer, your care team may run a test to examine your chromosomes, so they may learn more about their characteristics, which treatments may work, and your prognosis, or your outlook for recovery. One of the more common genetic tests is called the fluorescence in situ hybridization, or FISH, test.

Discovering any chromosomal changes in your cells helps doctors classify the type of cancer you have and find which drugs or treatments are most likely to succeed. Your doctor may recommend FISH testing periodically to gauge the course of your cancer treatment. In addition to FISH and cytogenetic testing, or testing to look for changes in chromosomes, other types of genetic tests include DNA sequencing, PCR (polymerase chain reaction) and gene expression microarrays.

What is a FISH test?

Your body contains all of the information to function within DNA molecules strung along the 46 chromosomes found in normal cells. Cancer cells, which behave in an abnormal way and grow out of control, may have noticeable changes in those chromosomes, including:

• Duplication. There may be extra copies of a portion of a chromosome, also called amplification.
• Deletion. There may be a portion missing.
• Inversion. A portion may be reversed.
• Translocation. A portion may have moved to another chromosome.
• Abnormal number of chromosomes. There may be an extra chromosome, or one missing.

How a FISH test works

In FISH testing, pieces of single-strand DNA (called DNA probes) are sent to find corresponding stretches of DNA from tumor cells sampled from the body. The probes, marked with a fluorescent dye, attach to those corresponding cells—that process is called hybridization. Once the probes attach to the chromosomes in the tumor cells, they glow when hit with fluorescent light, clearly showing where the probes match to the cancer cells, and where any chromosomal differences are.

Each of the three types of probes have separate uses:

• Locus-specific probes link to a certain spot on a chromosome. They may help pinpoint where a specific gene resides and the number of copies of that gene.
• Alphoid probes or centromeric repeat probes help determine the number of chromosomes. They may be combined with locus-specific probes to see whether any genetic material is missing from a chromosome.
• Whole chromosome probes use a combination of several probes with different color dyes to give a chromosome its own fluorescent signature. These may highlight abnormalities, such as translocation.

Test results

The FISH test produces results in a few days, unlike cytogenetic testing, another procedure that looks for chromosomal abnormalities but may take weeks. FISH testing may find many of the same abnormalities as cytogenetic testing and detect others too small to be picked up by cytogenetic testing.

What types of cancer is FISH used for?

Breast cancer: Breast tissue removed for a biopsy may undergo FISH testing to see whether it contains extra copies of the HER2 gene. All breast cells contain the HER2 protein on their surfaces, but cancer cells with higher-than-normal amounts of it often grow and spread faster than other forms of breast cancer. These forms of cancer are called HER2-positive cancer. Specific drugs are available to target the HER2 protein in these cancers.

Your care team may first use immunohistochemical, or IHC, stains to examine biopsied cells. IHC stains use antibodies, each of which attaches to a specific substance called an antigen on or inside a cell. The technique adds dyes to display a color in the presence of a certain antibody. It may be faster and more affordable than FISH testing, but sometimes both methods are used to get the clearest results.

IHC stain results:

• 0 or 1+, HER2-negative, indicates a cancer that may not respond to medicines targeting that protein.
• 2+, Uncertain, means FISH testing may be needed to get a better reading.
• 3+, HER2-positive, signals a cancer that will likely be treated with HER2 drugs.

Other cancers and uses: FISH testing has been used to diagnose and better determine the course and treatment of certain types of lung cancer, brain cancer, ovarian cancer, bladder cancer, colon cancer, prostate cancer, melanoma, leukemias, lymphomas and others.

It’s also used outside of cancer treatment and diagnosis—in research comparing the genes of related species, in diagnosing other diseases, and in reducing the chance of birth defects during in vitro fertilization (IVF).

How is the FISH test sample taken?

The type of cancer determines how it’s sampled for FISH analysis. For example, a bone marrow FISH test is used for multiple myeloma, while a urine FISH test is used for bladder cancer. Since any part of the body may develop cancer, biopsy methods include:

• Extracting tissue, blood or bone marrow through a needle
• Shaving off a thin piece of skin
• Taking a sample of tissue using an internal scope
• Removing an entire tumor, lymph node or organ through surgery

Preparing for your biopsy

Ahead of a biopsy, ask your doctor how to prepare, including whether you should avoid eating or drinking ahead of time or stop taking any medicines or supplements. Make sure your doctor knows your history of medical conditions and allergies, and speak up about any concerns or questions, including whether the procedure may cause scarring, pain or other risks.

Recovering from your biopsy

Recovery depends on the type of biopsy. You may be able to immediately return to normal activities, or you may need time to heal. If you were sedated or put under general anesthesia, someone else may need to drive you home after the procedure.

Contact your doctor if you have intense pain, bleeding, a fever or any other signs of infection after your procedure.