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Researchers call for wider implementation of FISH testing in metastatic breast cancer

February 26, 2003

Accurate diagnostic assessment of HER2 is essential for the effective treatment of metastatic breast cancer. Results to be published in the April issue of the Journal of Pathology indicate that FISH testing has many advantages over other methods, however in the UK there are very few diagnostic laboratories with the expertise to carry out the test. Researchers would like to see wider implementation of FISH testing.

HER2 is a member of the Epidermal Growth Factor receptor family, that is strongly overexpressed in metastatic breast cancer patients. The need for accurate and widely applicable approaches to HER2 diagnostics has recently increased due to the availability of a new anti-HER2 therapy, Herceptin, that has life-extending effects in women with HER2 overexpressing metastatic breast cancer but is of no benefit to those with HER2 negative disease.

Whilst many methodologies for HER2 testing have been reported in the literature, only two techniques are commonly used: immunohistochemistry (IHC) and fluorescence in situ hybridisation (FISH) which estimate protein expression and gene amplification respectively. IHC is widely used in many laboratories, but its results are dependent on the subjective interpretation of staining so the findings can be variable due to observer bias. The IHC test uses a 0 to 3+ scoring system, and those patients in the 2+ and 3+ are thought to benefit from Herceptin.

Researchers from three institutions, Royal Marsden Hospital, London, Glasgow Royal Infirmary and Nottingham City Hospital, studied 426 samples from 37 hospitals across the UK to look for correlation between the IHC and FISH analyses results.

The researchers, led by Professor Mitch Dowsett, found that for samples that were classified as IHC 0/1+ negative or IHC 3+ positive there was an excellent correlation with the FISH results. This shows that the IHC test is effective at identifying samples that fall into these extreme categories.

However, amongst the IHC 2+ tumours only 48% of the tumours were also FISH positive. This means that for 52% of the tumours the IHC test indicates that they would benefit from treatment with Herceptin whereas the FISH results show that they would not benefit from the treatment.

Current guidelines recommend that all IHC 2+ samples are checked by both IHC and FISH and according to Mitch Dowsett, "our results indicate that the performance of FISH on the IHC 2+ group is both necessary and sufficient for accurate determination of HER2 positive tumours."

"While Herceptin is restricted to metastatic breast cancer about 2,000 patients per year will require FISH testing but as this expands to the testing of patients at presentation with early disease, as is already happening, this number can be expected to greatly increase and it is essential that the laboratories are able to cope with the demand," says Mitch Dowsett.

In an editorial accompanying the article in the Journal of Pathology John Bartlett of Glasgow Royal Infirmary comments, "Although FISH has been shown to be effective, its application remains limited by the small number of centres where expertise is available. There is a strong case to be made for wider implementation of FISH testing to determine HER2 status in breast cancer, and this needs to be accompanied by better training and quality assurance schemes."

John Wiley & Sons