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Standardisation of EGFR FISH in colorectal cancer: results of an international interlaboratory reproducibility ring study
- Source :
- Journal of clinical pathology
- Publication Year :
- 2011
-
Abstract
- 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.
- Subjects :
- Oncology
Cancer Research
Pathology
medicine.medical_specialty
Colorado
Interlaboratory reproducibility
Colorectal cancer
Coefficient of variation
Gene Dosage
medicine.disease_cause
Gene dosage
Article
Pathology and Forensic Medicine
Predictive Value of Tests
Internal medicine
medicine
Biomarkers, Tumor
Panitumumab
Humans
Copy-number variation
Epidermal growth factor receptor
In Situ Hybridization, Fluorescence
Observer Variation
Cetuximab
medicine.diagnostic_test
biology
business.industry
Clinical Laboratory Techniques
Wild type
Reproducibility of Results
General Medicine
medicine.disease
Prognosis
ErbB Receptors
Europe
Predictive value of tests
Practice Guidelines as Topic
Cancer research
biology.protein
Fish
KRAS
Guideline Adherence
business
Colorectal Neoplasms
Chromosomes, Human, Pair 7
medicine.drug
Fluorescence in situ hybridization
Subjects
Details
- Language :
- English
- ISSN :
- 14724146 and 00219746
- Volume :
- 65
- Issue :
- 3
- Database :
- OpenAIRE
- Journal :
- Journal of clinical pathology
- Accession number :
- edsair.doi.dedup.....f7ddb2df324fe5e54c91a7de9a63ea45