What are the types of Fluorescence In Situ Hybridization (FISH) testing?

From the Guidelines

Fluorescence in situ hybridization (FISH) testing includes several types, primarily metaphase FISH and interphase FISH, which serve different diagnostic purposes, as outlined in the American College of Medical Genetics technical standards and guidelines 1. The main distinction between these types is the phase of the cell cycle in which the analysis is performed. Metaphase FISH is used to gain information about chromosome structure, often as an adjunct to conventional chromosome analysis, and is particularly useful for detecting microdeletions, cryptic rearrangements, and characterizing structural abnormalities 1. On the other hand, interphase FISH is utilized to detect and quantify specific genomic targets in non-dividing cells, making it practical for examining large numbers of cells and cells from samples with low or no mitotic index 1.

Some of the key applications of FISH testing include:

• Detection of aneuploidy in uncultured amniocytes
• Detection and quantification of abnormalities associated with neoplastic processes in hematological and solid tumor specimens
• Analysis of various sample types, including direct harvest or cultured fixed cells, aspirate smears, touch imprint preparations, cytospin preparations, and FFPE tissue sections, as detailed in the ACMG technical laboratory standards 2, 3

The choice of FISH test depends on the specific genetic abnormality being investigated, with applications spanning cancer diagnostics, prenatal testing, and the diagnosis of genetic disorders, and should be guided by the most recent and highest quality evidence, such as the 2024 ACMG technical laboratory standards 2, 3. In clinical practice, the selection of the appropriate FISH test type and sample preparation method is crucial for accurate diagnosis and management of genetic disorders. For instance, paraffin-embedded tissue, cultured or direct-harvest tumor cells, and cytospin preparations are all valid sample types for FISH analysis in the context of solid tumors, but each has its specific requirements and limitations, as outlined in the ACMG guidelines 3.

From the Research

FISH Testing Types

There are several types of FISH testing, including:

• Metaphase FISH: This type of FISH testing is used to examine chromosomal abnormalities and DNA damage on metaphase chromosomes 4.
• Interphase FISH: This type of FISH testing is used to study chromosome abnormalities in cancer and can be performed on different types of nuclei obtained from fresh and archived samples 5.
• Routine bone marrow cytogenetics: This type of testing is used to detect translocations and other chromosomal abnormalities in bone marrow cells 6.

Applications of FISH Testing

FISH testing has a wide range of applications, including:

• Detection of numerical chromosomal aberrations: FISH can be used to detect numerical chromosomal aberrations, such as trisomy 21, within a few hours 7.
• Study of genetic rearrangements: FISH can be used to study genetic rearrangements in human diseases 8.
• Tumor pathology: FISH can be used to identify specific chromosome aberrations in cancer and correlate them to prognosis and therapy 5.

Comparison of FISH Testing Types

Different types of FISH testing have different advantages and disadvantages, including:

• Metaphase FISH is feasible and straightforward compared to cytogenetics, but interphase FISH may be problematic 6.
• Interphase FISH is a high sensitivity technique, but it may not be able to identify subtle structural chromosomal abnormalities 7.