Fluorescence In Situ Hybridization, commonly known as FISH, is a laboratory technique used to detect and pinpoint specific DNA sequences within a cell’s chromosomes. This diagnostic tool helps identify genetic material and visualize chromosomal alterations, providing insights into a person’s genetic makeup.
Understanding How FISH Works
A FISH test uses specialized DNA probes. These short, single strands of DNA are designed to bind to specific, complementary DNA sequences on a chromosome. The probes are tagged with fluorescent dyes to make these target sequences visible.
Cells from a tissue or blood sample are prepared on a glass slide. The DNA within these cells is then unwound, separating its double-helix structure into single strands. Fluorescently labeled probes are introduced to the sample, and if complementary DNA sequences are present, the probes bind through hybridization.
Unbound probes are washed away. The slide is then examined under a special fluorescence microscope, which uses ultraviolet light to excite the fluorescent dyes. Areas where probes have bound glow with distinct colors, allowing visualization of specific genetic sequences or chromosomal regions. This helps identify the presence, absence, or structural changes of genes or chromosomal segments.
FISH in Cancer Detection and Treatment
FISH detects genetic abnormalities in cancer, such as gene amplifications (extra gene copies), chromosomal translocations (a piece of one chromosome attaches to another), and gene deletions (missing parts of a chromosome).
In breast cancer, FISH detects amplification of the HER2 gene. Increased HER2 gene copies lead to overexpression of the HER2 protein, which can cause breast cancer cells to grow and spread rapidly. Identifying HER2 amplification guides targeted therapies like trastuzumab.
FISH is also used in leukemias like chronic lymphocytic leukemia (CLL) and acute myeloid leukemia (AML). In acute promyelocytic leukemia, FISH detects a specific translocation between chromosomes 15 and 17. In CLL, FISH identifies deletions or mutations in the TP53 gene on chromosome 17, which indicates a less favorable response to standard chemotherapy and may suggest the use of different targeted therapies.
FISH can detect chromosomal translocations in other cancers, including lymphomas and sarcomas. In mantle cell lymphoma, FISH identifies the t(11;14) translocation involving the CCND1 gene. This information helps classify cancer, predict its behavior, and guide targeted therapies.
What Your FISH Test Results Mean
FISH test results are reported as positive, negative, or “equivocal.” A positive result indicates the presence of the specific genetic alteration. For example, a positive HER2 FISH test in breast cancer means the cancer cells have extra copies of the HER2 gene, making the tumor HER2-positive.
A negative FISH result means the specific genetic alteration was not found. For HER2 testing, a negative result means the HER2 gene is not amplified, indicating that HER2-targeted therapies may not be effective. An equivocal result means the findings are unclear and may require further testing or correlation with other diagnostic methods like immunohistochemistry (IHC).
Medical professionals interpret these results alongside other clinical findings and patient history. The presence or absence of specific genetic alterations influences a cancer diagnosis, provides insights into its aggressiveness, and helps determine suitable treatment strategies, including targeted therapies. FISH results are usually available within a few days, which can help expedite treatment planning.