Mutation analysis of KRAS prior to targeted therapy in colorectal cancer: development and evaluation of quality by a European external quality assessment scheme.

In Europe, the use of anti-EGFR monoclonal antibodies is restricted to Kirsten RAS (KRAS) wild-type colorectal tumors. Information on the KRAS status of the patients tumor is thus key for clinical practice; however, there is little guidance or definition on which KRAS mutations to assess and how to assess them. To ensure the consistency and the quality of KRAS test results in Europe, an interlaboratory control network needs to be set up. This pilot study aimed to identify the variables that need to be assessed in a quality control scheme and to provide a first assessment in a selected set of laboratories. Fourteen different tumor cases were circulated between 13 laboratories by a central laboratory acting as the referent for the mutation status determination. This study illustrated that of 13 experienced laboratories that perform KRAS testing only ten correctly identified the KRAS in all 14 cases that were circulated. There was no harmonization in DNA isolation and KRAS mutation detection method between the laboratories. These results indicate that future standardization is needed in KRAS mutation detection methodology. An expansion of the European Society of Pathology KRAS program could identify areas of difficulty in KRAS testing and provide the basis for harmonization.