Molecular Genetics External Quality Assessment Pilot Scheme for KRAS Analysis in Metastatic Colorectal Cancer
UK NEQAS for Molecular Genetics, Institute of Human Genetics, International Centre for Life, Central Parkway, Newcastle upon Tyne, United Kingdom. Genetic Testing and Molecular Biomarkers
(Impact Factor: 1.46).
08/2011; 15(11):777-83. DOI: 10.1089/gtmb.2010.0239
Laboratories are increasingly required to perform molecular tests for the detection of mutations in the KRAS gene in metastatic colorectal cancers to allow better clinical management and more effective treatment for these patients. KRAS mutation status predicts a patient's likely response to the monoclonal antibody cetuximab. To provide a high standard of service, these laboratories require external quality assessment (EQA) to monitor the level of laboratory output and measure the performance of the laboratory against other service providers. National External Quality Assurance Services for Molecular Genetics provided a pilot EQA scheme for KRAS molecular analysis in metastatic colorectal cancers during 2009. Very few genotyping errors were reported by participating laboratories; however, the reporting nomenclature of the genotyping results varied considerably between laboratories. The pilot EQA scheme highlighted the need for continuing EQA in this field which will assess the laboratories' ability not only to obtain accurate, reliable results but also to interpret them safely and correctly ensuring that the referring clinician has the correct information to make the best clinical therapeutic decision for their patient.
Available from: Sara Pizzamiglio
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The EC-funded project SPIDIA is aimed to develop evidence-based quality guidelines for the pre-analytical phase of blood samples used for DNA molecular testing. To this purpose, a survey and a pan-European External Quality Assessment (EQA) were implemented.
SPIDIA facility sent to all the participants the same blood sample to be processed without time or temperature limitation. DNA quality parameters performed at SPIDIA facility included: UV spectrophotometric analysis of DNA purity and yield, PCR interferences study by Kineret software and DNA integrity analysis by pulsed field gel electrophoresis.
197 applications have been collected from 30 European countries. A high variability of DNA fragmentation was observed whereas purity, yield and PCR interferences had a narrow distribution within laboratories. A significant difference between the RNase P single copy gene quantity obtained in the DNA samples extracted with the precipitation-based method respect to those obtained with beads and column-based methods was observed.
The results of this study will be the basis for implementing a second pan-European EQA and the results of both EQAs will be pooled and will provide the basis for the implementation of evidence-based guidelines for the pre-analytical phase of DNA analysis of blood samples.
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The clinical need to determine the presence of epidermal growth factor receptor (EGFR) gene mutations in non-small-cell lung cancers (NSCLC) in order to make informed decisions for patient treatment has seen the widespread introduction of EGFR molecular testing in many laboratories. To ensure high-quality molecular testing and allow laboratories to externally measure the standard of the service, an external quality assessment (EQA) scheme was provided to assess the whole testing process.
Formalin-fixed paraffin-embedded NSCLC tumour sections were distributed to laboratories for routine EGFR molecular testing, and the genotyping accuracy, interpretation of the result and clerical accuracy of the report were independently assessed.
Three rounds of assessment have identified many genotyping errors and have highlighted the need for external assessment and education in many testing laboratories. The main issues raised were the importance of accurate genotyping, including the use of common mutation nomenclature, clear unambiguous interpretation of the result, the impact of tumour sample assessment regarding amount of tumour being analysed and the heterogeneity of the sample on the molecular test result.
Improvements in all these areas were observed during the progression of the three EQA rounds, however, continuous unacceptably high genotyping error rates demonstrate the clear need for continual external assessment and education in this field.
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The detection of KRAS mutations is mandatory to initiate an anti-epidermal growth factor receptor (EGFR) antibody in the treatment of metastatic colorectal carcinoma (mCRC).
Patients and methods:
This observational retrospective study was performed in 160 French centres during a 2-week period in 2011. Its main objective was to evaluate the rate of KRAS testing in patients with mCRC having initiated their first-line therapy. Secondary objectives included time of process, techniques used and reasons for non-prescription.
Five hundred and thirty eight mCRC patients (67.1 ± 11.3 years, synchronous metastases: 69.9%) were enrolled in the study. KRAS testing was prescribed in 81.1% of patients, in a median of 15 days after the diagnosis of metastases, and of 15 days prior to the initiation of the first-line metastatic chemotherapy. KRAS status was available for 87% of patients, after 23.6 ± 28.2 days, but after the choice of the first-line therapy in 56.6% of patients. Heterogeneity of reception time was noteworthy within regions (8.3 ± 7 days to 38.8 ± 101 days). KRAS testing was not prescribed mainly due to the planned non-prescription of an anti-EGFR antibody.
This study confirmed that KRAS testing is definitely part of the management of most of mCRC patients, despite discrepancies observed in the rate of prescription and the time of results.
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