RT Journal Article
SR Electronic
T1 Standardisation of EGFR FISH in colorectal cancer: results of an international interlaboratory reproducibility ring study
JF Journal of Clinical Pathology
JO J Clin Pathol
FD BMJ Publishing Group Ltd and Association of Clinical Pathologists
SP 218
OP 223
DO 10.1136/jclinpath-2011-200353
VO 65
IS 3
A1 Sartore-Bianchi, Andrea
A1 Fieuws, Steffen
A1 Veronese, Silvio
A1 Moroni, Mauro
A1 Personeni, Nicola
A1 Frattini, Milo
A1 Torri, Valter
A1 Cappuzzo, Federico
A1 Borght, Sara Vander
A1 Martin, Vittoria
A1 Skokan, Margaret
A1 Santoro, Armando
A1 Gambacorta, Marcello
A1 Tejpar, Sabine
A1 Varella-Garcia, Marileila
A1 Siena, Salvatore
YR 2012
UL http://jcp.bmj.com/content/65/3/218.abstract
AB Aims Epidermal growth factor receptor (EGFR) gene copy number evaluated by fluorescence in situ hybridisation (FISH) can discriminate among KRAS wild-type patients those with better outcome to EGFR-targeted therapy in metastatic colorectal cancer, further enhancing selection of patients. Nevertheless, enumeration of gene copies is challenging and the lack of analytical standardisation has limited incorporation of the test into the clinical practice. We therefore assessed EGFR FISH interlaboratory consensus among five molecular diagnostic reference centres.Methods A set of 12 colorectal cancer samples circulated among laboratories, and samples were scored according to commonly agreed guidelines. Reproducibility was quantified using the standard error of measurement (SEM).Results A SEM of 0.865 and a within-subject coefficient of variation (WSCV) of 26.8% for mean EGFR gene/nuclei and a SEM of 0.235 and a WSCV of 19.4% for the mean EGFR gene/CEP7 ratio were observed. Measurement of the fraction of cells displaying chromosome 7 polysomy showed WSCV of 46.6%, 34.0% and 51.0% for percentage of cells displaying ≤2, ≥3 and ≥4 EGFR signals, respectively. Among different slides of the same specimen, the WSCV was 6.1% for mean EGFR gene/nuclei and 3.9% for mean of EGFR gene/CEP7 ratios.Conclusions Molecular diagnosis of EGFR gene copy number by FISH varied largely among pathology centres, with fluctuations covering the whole range of proposed cut-offs of predictive usefulness from literature. Definition of a detailed scoring system and implementation of comprehensive training programmes for laboratories are therefore necessary before including the test into clinical practice.