FISH test is a microscopic chromosome test used in prenatal and carcinoma diagnosis of breast cancer, gastric cancer and in chronic lymphocytic leukemia. The test, the result of which is available within 1 to 2 days, can detect mainly chromosomal abnormalities that are due to an altered chromosome set of certain chromosomes. The test is performed exclusively as a companion or preliminary test for a detailed chromosome analysis, the results of which may not be available until 2 to 3 weeks after the cells are harvested.
What is the FISH test?
In the test, the result of which is available within 1 to 2 days, it is possible to detect mainly chromosomal abnormalities that are due to an altered set of chromosomes of certain chromosomes. The FISH test (fluorescence in situ hybridization) in prenatal diagnostics allows conclusions to be drawn about an altered chromosome set in the case of certain chromosomes. To perform the FISH test, at least 50 non-cultured fetal cells (amniotic cells) taken from the amniotic fluid (approx. 2 – 3 ml) are required. An alternative method for obtaining suitable cells is chorionic villus sampling, in which cells are taken by biopsy from the region of the umbilical cord attachment. A special procedure allows the individual strands of chromosomes 13, 18, 21 and the X and Y chromosomes to be distinguished from each other by fluorescent colors, so that any trisomy present is indicated by the presence of three instead of two homologous strands of a chromosome. In gastric and breast cancer, the FISH test can be used to check whether the tumor has more than two copies of the HER2/neu gene (human epidermal growth factor receptor), which has consequences for the type of chemotherapy. In chronic lymphocytic leukemia disease, multiple FISH test analyses of bone marrow and peripheral blood samples can identify the most common chromosomal shifts at specific genes, which also has implications for therapy.
Function, effect, and goals
Chromosomes in isolated nuclei are induced to split their double-helix structure by a special chemical treatment or by exposure to heat, and chromosome-specific DNA probes, each with its complementary DNA sequence, connect to “their” specific chromosomes. The DNA probes are labeled with different fluorescent colors so that special software can be used to distinguish the labeled chromosomes from each other and count them in an automated process. Known are e.g. trisomies, in which three instead of two chromosome strands are found for one chromosome. So-called monosomies are also known, in which only one strand of the X chromosome is present as well as three or four homologous strands of all chromosomes. The most important chromosomal abnormalities that can be detected by FISH test in prenatal diagnosis are Ullrich Turner syndrome (monosomy X), triple X syndrome (trisomy or polysomy X), Klinefelter syndrome, in which an extra X chromosome (XXY instead of XY) is present in all or part of the somatic cells in boys, Down syndrome (trisomy 21), Edwards syndrome (trisomy 18), and Pätau syndrome (trisomy 13). Monosomy X, in which girls have only one X chromosome, is usually lethal, which means that in about 98% of cases it leads to miscarriage within the first three months of pregnancy. In the event that a birth still occurs, the girls have a normal life expectancy, are of average intelligence, but often suffer from a number of malformations of internal organs and are usually infertile. Triple X syndrome with chromosome set XXX) also affects only girls. Normal pregnancy and birth are possible. The mostly tall women with the triple X chromosome can live normally and usually show no physical abnormalities, but learning difficulties are not uncommon and problems with fine motor skills occur. Klinefelter syndrome, which can affect only boys and men, is characterized by an extra X chromosome that is present in all body cells or only partially. Physical characteristics include above-average height with unusually long arms and legs. Klinefelter syndrome usually results in decreased testicular growth with decreased testosterone secretion.Down syndrome, synonymous with trisomy 21, is usually associated with certain physical characteristics and with cognitive impairment. There are different forms of trisomy 21, of which the so-called free trisomy 21 is predominant with about 95% of cases. Trisomy 18 (Edwards syndrome) results in miscarriage in most cases, is associated with a variety of physical features, and life expectancy is only a few days. Trisomy 13 (Pätau syndrome) is also characterized by a variety of physical features and abnormalities, and in many cases results in miscarriage or stillbirth. The life expectancy for delivered children is only a few years. The aim of prenatal FISH testing is to detect known chromosomal abnormalities at an early stage in order to offer parents the alternative of a legal abortion to carry the child to term. In the case of breast and liver cancers, the carcinomas can be checked for an increased number of the HER2/neu gene by means of FISH testing. If positive, there is increased production of growth factor receptors that respond to certain chemotherapies. FISH tests are also available for the detection of specific gene abnormalities in chronic lymphocytic leukemia (CLL), which improve the assembly of effective agents for chemotherapy.
Risks, side effects, and hazards
The FISH test itself is not associated with any risks or hazards. Only the collection of the cells to be examined by biopsy or by amniocentesis are associated with minor risks of infection due to their invasive nature. The peculiarity is that although the FISH test can detect some specific chromosomal aberrations, it is not certain that there are no chromosomal aberrations in the case of a negative result, since not all abnormalities can be detected by the FISH test. In the case of a positive test result, further diagnostic procedures should follow to confirm or reject the result as false.
