RAS testing for colorectal cancer patients is reliable in European laboratories that pass external quality assessment

Virchows Arch. 2018 May;472(5):717-725. doi: 10.1007/s00428-017-2291-z. Epub 2018 Jan 15.


Wild-type status of KRAS and the NRAS gene (exon 2, 3, and 4) in the tumor should be determined before treatment of metastatic colorectal cancer (mCRC) patients with EGFR-targeting agents. There is a large variation in test methods to determine RAS status, and more sensitive detection methods were recently introduced. Data from quality assessment programs indicate substantial error rates. This study assessed the completeness and correctness of RAS testing in European laboratories that successfully passed external quality assessment (EQA). Participants were requested to send material of their most recent ten patients with mCRC who had been tested for RAS status. Isolated DNA, a hematoxylin and eosin stained tissue slide with a marked area for macrodissection and accompanying patient reports were requested. Samples were reevaluated in a reference laboratory by using a next-generation sequencing approach. In total, 31 laboratories sent in the requested material (n = 309). Despite regulations for anti-EGFR therapy, one institute did not perform full RAS testing. Reanalysis was possible for 274 samples with sufficient DNA available. In the hotspot codons of KRAS and NRAS, seven discordant results were obtained in total, five of them leading to a different prediction of anti-EGFR therapy efficacy (2%; n = 274). Results show that oncologists can rely on the quality of laboratories with good performance in EQA. Oncologists need to be aware that the testing laboratory participates successfully in EQA programs. Some EQA providers list the good performing laboratories on their website.

Keywords: Biological markers; Colorectal neoplasms; Molecular pathology; Quality assurance; Reproducibility.

MeSH terms

  • Colorectal Neoplasms / genetics*
  • GTP Phosphohydrolases / analysis*
  • GTP Phosphohydrolases / genetics
  • Genetic Testing / standards
  • Humans
  • Medical Oncology / standards*
  • Membrane Proteins / analysis*
  • Membrane Proteins / genetics
  • Proto-Oncogene Proteins p21(ras) / analysis*
  • Proto-Oncogene Proteins p21(ras) / genetics
  • Quality Assurance, Health Care*


  • KRAS protein, human
  • Membrane Proteins
  • GTP Phosphohydrolases
  • NRAS protein, human
  • Proto-Oncogene Proteins p21(ras)