Diagnostic tests

 

EGFR - FISH Testing for Gene Copy Number                                           

 

In non-small-cell lung cancer there is compelling evidence that response to both gefitinib (Iressa™) and erlotinib (Tarceva™) is associated with EGFR gene copy number, as well as with the presence of certain activating mutations of the EGFR gene. The picture is less clear with respect to the expression of the receptor protein itself, and the use of immunohistochemistry to evaluate levels of expression is of questionable utility.

 In colorectal cancer there is also evidence that response to the EGFR-targeting antibody treatments cetuximab (Erbitux™) and panitumumab (Vectibix™) is linked to gene copy number, as detected by Fluorescence In Situ Hybridisation (FISH). In addition, for these agents it is suggested that they are suitable only for patients who demonstrate over-expression of EGFR protein, as detected by immunohistochemistry.

          

 EGFR FISH.png

A breast tumour processed for EGFR FISH. Copies of the EGFR gene are seen as red dots against the deep blue of individual cell nuclei. The red spots represent markers for chromosome 7. In a normal cell there is usually 2 copies of each.

 Evaluation

Source BioScience offers a validated, standardised EGFR FISH test, which can be used to demonstrate EGFR gene amplification or increased copy number due to polysomy. FISH evaluation to identify EGFR gene amplification is assessed visually over a number of representative areas within the sample to account for heterogeneity. The sample is assigned a score in the form of a ratio, relating the number of copies of the EGFR gene to the number of copies of chromosome 7. A score of >2 indicates gene amplification.

  

References:

Cappuzzo et al. (2005) Epidermal Growth Factor Receptor gene and protein and gefitinib sensitivity in non-small-cell lung cancer. J Natl Cancer Inst 97:643

Moroni et al. (2005) Gene copy number for epidermal growth factor receptor (EGFR) and clinical response to antiEGFR treatment in colorectal cancer: a cohort study. Lancet Oncol 6:279

© Medical Solutions 2009