ORIGINAL ARTICLE

External quality assurance of HER2 fluorescence in situ hybridisation testing: results of a UK NEQAS pilot scheme

John M S Bartlett¹, Merdol Ibrahim², Keith Miller², Bharat Jasani³, John M Morgan³, Ian Ellis⁴, Elaine Kay⁵, Hilary Magee⁶ and Sarah Barnett⁷

¹ Endocrine Cancer Group, Edinburgh Cancer Research Centre, Western General Hospital, Edinburgh, UK
² UK National External Quality Assessment Scheme, University College London, London, UK
³ Department of Pathology, School of Medicine, Cardiff University, Cardiff, UK
⁴ University of Nottingham, Molecular Medical Sciences, Department of Histopathology, Nottingham City Hospital, Nottingham, UK
⁵ Department of Histopathology, Beaumont Hospital and The Royal College of Surgeons in Ireland, Beaumont Hospital, Dublin, Ireland
⁶ Adelaide and Meath Hospital, incorporating the National Children’s Hospital, Dublin, Ireland
⁷ University College London, Advanced Diagnostics, London, UK

Correspondence to:
Correspondence to:
Dr J M S Bartlett
Endocrine Cancer Group, Edinburgh Cancer Research Centre, Western General Hospital, Crewe Road South, Edinburgh EH4 2XR, UK; John.Bartlett{at}ed.ac.uk

Background and Aims: Trastuzumab provides clinical benefit for advanced and early breast cancer patients whose tumours over-express or have gene amplification of the HER2 oncogene. The UK National External Quality Assessment Scheme (NEQAS) for immunohistochemical testing was established to assess and improve the quality of HER2 immunohistochemical testing. However, until recently, no provision was available for HER2 fluorescence in situ hybridisation (FISH) testing. A pilot scheme was set up to review the performance of FISH testing in clinical diagnostic laboratories.

Methods: FISH was performed in 6 reference and 31 participating laboratories using a cell line panel with known HER2 status.

Results: Using results from reference laboratories as a criterion for acceptable performance, 60% of all results returned by participants were appropriate and 78% either appropriate or acceptable. However, 22.4% of results returned were deemed inappropriate, including 13 cases (4.2%) where a misdiagnosis would have been made had these been clinical specimens.

Conclusions: The results of three consecutive runs show that both reference laboratories and a proportion of routine clinical diagnostic (about 25%) centres can consistently achieve acceptable quality control of HER2 testing. Data from a significant proportion of participating laboratories show that further steps are required, including those taken via review of performance under schemes such as NEQAS, to improve quality of HER2 testing by FISH in the "real world".

Abbreviations: FISH, fluorescence in situ hybridisation; NEQAS, National External Quality Assessment Scheme

Keywords: HER2/erbB-2; FISH/in situ hybridisation; fluorescence; herceptin; trastuzumab; quality assurance

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