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Arch Pathol Lab Med. 2019 Apr 10. doi: 10.5858/arpa.2018-0396-CP. [Epub ahead of print]

Performance Comparison of Different Analytic Methods in Proficiency Testing for Mutations in the BRAF, EGFR, and KRAS Genes: A Study of the College of American Pathologists Molecular Oncology Committee.

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From the Office of the Director, The Joint Pathology Center, Silver Spring, Maryland (Dr Moncur); the Department of Pathology, St Joseph Mercy Hospital, Ypsilanti, Michigan (Dr Bartley); the Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha (Dr Bridge); the Department of Pathology, University Health Network, University of Toronto, Toronto, Ontario, Canada (Dr Kamel-Reid); the Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston (Dr Lazar); the Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts (Drs Lindeman and Kim); Biostatistics (Mr Long) and Proficiency Testing (Ms Vasalos), College of American Pathologists, Northfield, Illinois; the Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill (Dr Merker); the Department of Pathology and Cell Biology, Columbia University Medical Center, New York, New York (Dr Rai); the Department of Pathology, Yale University School of Medicine, New Haven, Connecticut (Dr Rimm); and the Department of Pathology and Laboratory Medicine, Strong Memorial Hospital, University of Rochester Medical Center and Pathology and Laboratory Medicine, Molecular Diagnostic Laboratory, Rochester, New York (Dr Rothberg).
Dr Moncur is employed by the US Army. The identification of specific products or scientific instrumentation is considered an integral part of the scientific endeavor and does not constitute endorsement or implied endorsement on the part of the authors, the Department of Defense, or any component agency. The views expressed in this article are those of the authors and do not reflect the official policy of the Department of Army/Navy/Air Force, Department of Defense, or US government. The other authors have no relevant financial interest in the products or companies described in this article.



The performance of laboratory testing has recently come under increased scrutiny as part of important and ongoing debates on regulation and reimbursement. To address this critical issue, this study compares the performance of assay methods, using either commercial kits or assays designed and implemented by single laboratories ("home brews"), including next-generation sequencing methods, on proficiency testing provided by the College of American Pathologists Molecular Oncology Committee.


To compare the performance of different assay methods on College of American Pathologists proficiency testing for variant analysis of 3 common oncology analytes: BRAF, EGFR, and KRAS.


There were 6897 total responses across 35 different proficiency testing samples interrogating 13 different variants as well as wild-type sequences for BRAF, EGFR, and KRAS. Performance was analyzed by test method, kit manufacturer, variants tested, and preanalytic and postanalytic practices.


Of 26 reported commercial kits, 23 achieved greater than 95% accuracy. Laboratory-developed tests with no kit specified demonstrated 96.8% or greater accuracy across all 3 analytes (1123 [96.8%] acceptable of 1160 total responses for BRAF; 848 [97.5%] acceptable of 870 total responses for EGFR; 942 [97.0%] acceptable of 971 total responses for KRAS). Next-generation sequencing platforms (summed across all analytes and 2 platforms) demonstrated 99.4% accuracy for these analytes (165 [99.4%] acceptable of 166 total next-generation sequencing responses). Slight differences in performance were noted among select commercial assays, dependent upon the particular design and specificity of the assay. Wide differences were noted in the lower limits of neoplastic cellularity laboratories accepted for testing.


These data demonstrate the high degree of accuracy and comparable performance across all laboratories, regardless of methodology. However, care must be taken in understanding the diagnostic specificity and reported analytic sensitivity of individual methods.


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