29 June 2023

Ever heard of FISH testing? No, not that type of fish - Fluorescence in Situ Hybridisation (FISH). 

Sometimes the chromosomes in a cell will rearrange themselves with devastating effects. Rearrangements can be subtle, like duplication or deletion of a small part of the chromosome, and hard to see with conventional testing.

One way to detect changes and rearrangements in chromosomes is to FISH. The position of DNA sequences in chromosomes can be found using fluorescent probes. If the probe's relative position differs from where this would be in a healthy cell, the chromosome has been rearranged.

There are several uses for FISH on DNA. One situation in which chromosomes are rearranged regularly are in tumours or suspected tumours, and pathologists investigating tissue for evidence of tumours will often use FISH to look for evidence of chromosome rearrangements.

"An advantage to this testing is that it doesn’t require a lot of tissue and you can correlate it very well with the histology to ensure you’re testing the tumour," says Dr Alexandra Jolley, a Consultant Pathologist in Anatomical Pathology/Surgical Pathology with partial scope of practice in Molecular Genetics.

Collaboration is Key

SA Pathology began FISH testing in the late eighties within the cytogenomic section of the Genetics and Molecular Pathology (GMP) directorate. The service has grown considerably and, in 2021 our Anatomical Pathology (AP) team at the Royal Adelaide Hospital (RAH) partnered with GMP to provide FISH of solid tumours.

Together, Maria Collis, Acting Directorate Manager of AP, Drs. Alexandra Jolley and Dariusz Ladon, Head of Cytogenomics at GMP, Jennifer Gil, Lead Medical Scientist, AP, and Yejin Chang, a University of South Australia graduate who was recently appointed as a medical scientist, work to provide our patients with a first-rate FISH service. Yejin is in the process of getting trained as a second reporting AP FISH scientist.

Co-location of the Anatomical Pathology scientists and pathologists with the FISH testing has proven vital for the diagnostic process.

Alex says, "Being able to do histology and FISH in one laboratory saves double handling and streamlines the workflow. We’re also able to use pathologists’ correlation with morphology to ensure that we’re testing the tumour, and we can prioritise the urgent cases."

It’s a partnership that continues to stay strong with improved outcomes combining both cytogenetics and histology expertise within the organisation.

Targeted testing

FISH testing is used for diagnostic and treatment purposes. It is necessary to have an inkling of what chromosome/gene is rearranged or copy number altered so that probes that bind to informative locations on the chromosome can be chosen. Pathologists will sometimes request FISH testing for specific genetic rearrangements/copy number changes to help support or revoke a diagnosis considered based on clinical information and findings from

light microscopy, electron microscopy, special stains and immunohistochemistry. FISH is also used to determine if a patient’s tumour is likely to respond to targeted drug therapy, and reflex testing is performed pending immunohistochemical studies for some tumours like non-small cell lung cancer.

Each probe marks a specific location on a chromosome and must be vigorously tested and validated.

Jennifer says that validating a probe to NATA standards,"involves confirming expected results for many different normal cases to establish reference ranges for the normal chromosomal location, before being tested on multiple positive cases (cases with a rearranged chromosome) to ensure the probe is functioning and doing what it should."

Using FISH as a diagnostic tool is a team effort. Dariusz likens the process to completing a jigsaw puzzle.

"Everyone has a piece, and when the patient gets their final results and prognosis – they receive the full picture. This means they can be treated promptly."

Streamlined care

Turnaround times are a key focus for the team as they can impact patient treatment.

The team prioritises cases where results will affect the chemotherapy treatment regime, or where it will affect diagnosis and disease management.

Maria also says being able to integrate all of the data into a single report helps and allows the requesting clinician to see all the relevant information in one report (all the pieces of the puzzle to which Dariusz refers to).

AP and GMP have established a single database to ensure traceability in all aspects of testing. Maria credits this achievement to the crucial behind-the-scenes work being done by Chris Bodel AP’s Subject Matter Expert (SME) and many others across the organisation.

Partnering for success

Dariusz is extremely grateful for the partnership, saying it has streamlined both areas’ workflows.

Maria also believes the collaboration is providing massive benefits to AP for their up-and-coming scientists.

After graduating from university, these students put their abilities to use and are proud to collaborate with some of the best pathologists in the field and provide patient care. It is challenging but also rewarding to use their scientific expertise to validate new probes.

Recently, the team has added a new validated probe to their library that can be used in soft tissue and bone tumours, helping to differentiate between benign and malignant entities.

Their probes have also gone on to be used in clinical trials, to find targeted treatment solutions for Australians.

Alex says,"This work is a really nice example of the Anatomical Pathology and the Genetics and Molecular Pathology directorates working synergistically for better patient outcomes."

If you’d like to learn more about FISH testing, read this interesting article from Nature Journal.

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