PRENATAL ANEUPLOIDY DETECTION IN INTERPHASE CELLS BY FLUORESCENCE IN-SITU HYBRIDIZATION (FISH)

FISH is a quick, inexpensive, accurate, sensitive and relatively speci fic method for aneuploidy detection in samples of uncultured chorionic villus cells and amniotic fluid cells. FISH allows detection of the a utosomal trisomies 13, 18 and 21 and X and Y abnormalities and any oth er chromosome abnormality for which a specific probe is available. The detection rate of these abnormalities is high in informative samples which have a concordance of >99.5% with cytogenetic results. A relativ ely high number of abnormal cases are found in uninformative samples. However, such samples should be regarded as samples to be investigated further. Clinical experience with the use of FISH for prenatal diagno sis is now beyond 10,000 cases; a number of clinical protocols and sma ller trials have also been carried out, resulting in 90% of attempted analyses giving informative results with a high detection rate and ext raordinarily low false-positive and false-negative rates Unsolved prob lems remain, such as occasional technical failures, admixtures of mate rnal blood and up to 20% uninformative scoring results, especially for abnormal specimens. FISH is at present used as an adjunct to classica l cytogenetic analysis. However, this should not be interpreted as mea ning that FISH could not be used as a methodology in its own right. If FISH were to be considered a diagnostic test then this might be the c ase, due to the risk of false-negative and false-positive results and the fact that FISH does not allow a diagnosis of certain structural ab normalities. If, on the other hand, FISH is considered a screening tes t, which means that in all abnormal (or indeterminate) cases, classica l cytogenetic analysis would follow the abnormal screening test, the a ccuracy which is potentially higher than for other screening methods, for example in cases of trisomy 21, justifies FISH as a prenatal scree ning lest in its own right.