1. RAS testing in metastatic colorectal cancer : Excellent reproducibility amongst 17 Dutch pathology centers
- Author
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Boleij, Annemarie, Tops, Bastiaan B J, Rombout, Paul D.M., Dequeker, Elizabeth M., Ligtenberg, Marjolijn J. L., van Krieken, J. Han, van Noesel, Carel J M, Scheidel-Jacobse, Karen C., Kummer, J. A., Roepman, P., Prinsen, C.F.M., van den Berg-van Erp, S. H.M., van Gorp, J. M.H.H., Nederlof, Petra M., Caspers, E., Dinjens, Winand N M, Beerens, E. C.W., 't Hart, N. A., van den Brule, Adriaan J. C., van der Geize, R., Riemersma, S. A., van Wezel, T., Morreau, H., van Eijk, R., Jeuken, J. W.M., Dirkx, A., Klomp, J.M., van Blokland, W. T.M., ter Elst, A., Schuuring, E., Diepstra, A., Heideman, Danielle A. M., van Grieken, Nicole C. T., Sie, D., Targeted Gynaecologic Oncology (TARGON), Damage and Repair in Cancer Development and Cancer Treatment (DARE), Stem Cell Aging Leukemia and Lymphoma (SALL), and Guided Treatment in Optimal Selected Cancer Patients (GUTS)
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Neuroblastoma RAS viral oncogene homolog ,Pathology ,Colorectal cancer ,Cancer development and immune defence Radboud Institute for Molecular Life Sciences [Radboudumc 2] ,WILD-TYPE KRAS ,THERAPY ,GTP Phosphohydrolases ,Metastasis ,Tumours of the digestive tract Radboud Institute for Molecular Life Sciences [Radboudumc 14] ,Medicine ,University medical ,Netherlands ,Molecular pathology ,Antibodies, Monoclonal ,High-Throughput Nucleotide Sequencing ,CETUXIMAB ,ErbB Receptors ,Oncology ,TRIAL ,Colorectal Neoplasms ,Proto-Oncogene Proteins B-raf ,medicine.medical_specialty ,Antineoplastic Agents ,Primary care ,Rare cancers Radboud Institute for Molecular Life Sciences [Radboudumc 9] ,Reference laboratory ,ASSURANCE ,PANITUMUMAB ,Proto-Oncogene Proteins p21(ras) ,PERCENTAGE ,Next generation sequencing ,External quality assessment ,Humans ,Genetic Testing ,EXTERNAL-QUALITY-ASSESSMENT ,Base Sequence ,business.industry ,MUTATIONS ,Membrane Proteins ,Quality control ,Sequence Analysis, DNA ,medicine.disease ,digestive system diseases ,Mutation ,RAS Mutation ,CELLS ,Clinical Research Paper ,business ,RAS - Abstract
// Annemarie Boleij 1 , Bastiaan B.J. Tops 2 , Paul D.M. Rombout 1 , Elizabeth M. Dequeker 3 , Marjolijn J.L. Ligtenberg 1,2 , J. Han van Krieken 1 and Dutch RAS EQA Initiative 4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20 1 Department of Pathology, Radboud University Medical Center, Nijmegen, The Netherlands 2 Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands 3 Department of Public Health and Primary Care, Biomedical Quality Assurance Research Unit, KU Leuven - University of Leuven, Leuven, Belgium 4 C.J.M. van Noesel, Academic Medical Center (AMC), Department of Pathology, Amsterdam 5 C.C. Scheidel-Jacobse (Technical specialist), J.A. Kummer (Pathologist/KMBP), P. Roepman (KMBP in training), St. Antonius Ziekenhuis, Department of Pathology, Nieuwegein 6 C.F.M. Prinsen (KMBP), S.H.M. van den Berg-van Erp (Pathologist), Canisius Wilhelmina Ziekenhuis (CWZ), Department of Pathology, Nijmegen 7 J.M.H.H. van Gorp, Diakonessenhuis, Laboratory for Pathology, Utrecht 8 P.M. Nederlof, Dutch Cancer Institute (NKI), Amsterdam. 9 E. Caspers, St. Elisabeth Ziekenhuis, Department of Molecular Pathology, Tilburg 10 W.N.M. Dinjens, E.C.W. Beerens, Erasmus MC, Department of Pathology, Molecular Diagnostics, Rotterdam 11 N.A. ‘t Hart, Isala, Department of Pathology, Zwolle 12 A.J.C. van den Brule, Jeroen Bosch Ziekenhuis, Molecular Diagnostics, ‘s-Hertogenbosch 13 R. van der Geize (KMBP), S.A. Riemersma (Pathologist), Laboratory for Pathology Oost-Nederland (LABPON), Hengelo 14 T. van Wezel (KMBP), H. Morreau (Pathologist), R. van Eijk (Technical specialist), Leiden University Medical Center (LUMC), Department of Pathology, Leiden 15 J.W.M. Jeuken, Laboratory for Pathology and Medical Microbiology (PAMM), Eindhoven 16 A. Dirkx, Pathan B.V., Molecular Diagnostics, Rotterdam 17 M. Klomp, Rijnstate Ziekenhuis, Department of Pathology, Arnhem 18 W.T.M van Blokland, University Medical Center (UMC) Utrecht, Molecular Pathology, Utrecht 19 A. ter Elst (Technical specialist/KMBP in training), E. Schuuring (KMBP), A. Diepstra (Pathologist), University Medical Center Groningen (UMCG), Department of Pathology, Groningen 20 D.A.M. Heideman (KMBP), N.C.T. van Grieken (Pathologist), D. Sie (Technical specialist), VU-University Medical Center (VUMC), Department of Pathology, Amsterdam Correspondence to: J.Han van Krieken, email: // Keywords : RAS, colorectal cancer, metastasis, quality control, next generation sequencing Received : February 09, 2015 Accepted : March 18, 2015 Published : April 12, 2015 Abstract In 2013 the European Medicine Agency (EMA) restricted the indication for anti-EGFR targeted therapy to metastatic colorectal cancer (mCRC) with a wild-type RAS gene, increasing the need for reliable RAS mutation testing. We evaluated the completeness and reproducibility of RAS -testing in the Netherlands. From 17 laboratories, tumor DNA of the first 10 CRC cases tested in 2014 in routine clinical practice was re-tested by a reference laboratory using a custom next generation sequencing panel. In total, 171 CRC cases were re-evaluated for hotspot mutations in KRAS , NRAS and BRAF . Most laboratories had introduced complete RAS -testing (65%) and BRAF -testing (71%) by January 2014. The most employed method for all hotspot regions was Sanger sequencing (range 35.7 – 49.2%). The reference laboratory detected all mutations that had been found in the participating laboratories ( n = 92), plus 10 additional mutations. This concerned three RAS and seven BRAF mutations that were missed due to incomplete testing of the participating laboratory. Overall, the concordance of tests performed by both the reference and participating laboratory was 100% (163/163; κ-static 1.0) for RAS and 100% (144/144; κ-static 1.0) for BRAF . Our study shows that RAS and BRAF mutations can be reproducibly assessed using a variety of testing methods.
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- 2015