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Higher quality of molecular testing, an unfulfilled priority: Results from external quality assessment for KRAS
Lien Tembuyser1, Marjolijn J L Ligtenberg2, Nicola Normanno3
1Biomedical Quality Assurance Research Unit, Department of Public Health and Primary Care, KU Leuven-University of Leuven, Leuven, Belgium.
Abstract:
Precision medicine is now a key element in clinical oncology. RAS mutational status is a crucial predictor of responsiveness to anti-epidermal growth factor receptor agents in metastatic colorectal cancer. In an effort to guarantee high-quality testing services in molecular pathology, the European Society of Pathology has been organizing an annual KRAS external quality assessment program since 2009. In 2012, 10 formalin-fixed, paraffin-embedded samples, of which 8 from invasive metastatic colorectal cancer tissue and 2 artificial samples of cell line material, were sent to more than 100 laboratories from 26 countries with a request for routine KRAS testing. Both genotyping and clinical reports were assessed independently. Twenty-seven percent of the participants genotyped at least 1 of 10 samples incorrectly. In total, less than 5% of the distributed specimens were genotyped incorrectly. Genotyping errors consisted of false negatives, false positives, and incorrectly genotyped mutations. Twenty percent of the laboratories reported a technical error for one or more samples. A review of the written reports showed that several essential elements were missing, most notably a clinical interpretation of the test result, the method sensitivity, and the use of a reference sequence. External quality assessment serves as a valuable educational tool in assessing and improving molecular testing quality and is an important asset for monitoring quality assurance upon incorporation of new biomarkers in diagnostic services.
Insights
External quality assessment for KRAS testing in metastatic colorectal cancer revealed significant genotyping errors and missing clinical interpretations. This highlights the need for improved molecular pathology services to ensure accurate precision medicine in oncology.
Area of Science:
- Oncology
- Molecular Pathology
- Clinical Diagnostics
Background:
- Precision medicine relies on accurate molecular diagnostics, with RAS mutational status being critical for anti-EGFR therapy in metastatic colorectal cancer (mCRC).
- The European Society of Pathology established an annual KRAS external quality assessment (EQA) program to ensure high-quality molecular pathology testing services.
Purpose of the Study:
- To assess the quality of routine KRAS testing provided by laboratories participating in the 2012 EQA program.
- To identify common genotyping errors and deficiencies in clinical reporting for KRAS mutations in mCRC.
Main Methods:
- Ten samples (8 mCRC tissue, 2 cell line) were distributed to over 100 laboratories across 26 countries for routine KRAS testing.
- Genotyping results and clinical reports were independently evaluated for accuracy and completeness.
Main Results:
- Twenty-seven percent of laboratories incorrectly genotyped at least one sample, with errors including false negatives, false positives, and misidentified mutations.
- Less than 5% of all distributed specimens had genotyping errors.
- Twenty percent of laboratories reported technical errors, and many clinical reports lacked essential elements like clinical interpretation and method sensitivity.
Conclusions:
- The KRAS EQA program identified substantial room for improvement in molecular testing quality for mCRC.
- EQA is crucial for identifying and rectifying errors, serving as an educational tool to enhance diagnostic services.
- Standardization and quality assurance are vital as new biomarkers are integrated into clinical practice.
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