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. 2011;16(4):467-78.
doi: 10.1634/theoncologist.2010-0429. Epub 2011 Mar 26.

External quality assessment for KRAS testing is needed: setup of a European program and report of the first joined regional quality assessment rounds

Ellen Bellon  1 , Marjolijn J L Ligtenberg, Sabine Tejpar, Karen Cox, Gert de Hertogh, Karin de Stricker, Anders Edsjö, Vassilis Gorgoulis, Gerald Höfler, Andreas Jung, Athanassios Kotsinas, Pierre Laurent-Puig, Fernando López-Ríos, Tine Plato Hansen, Etienne Rouleau, Peter Vandenberghe, Johan J M van Krieken, Elisabeth Dequeker
Affiliations

External quality assessment for KRAS testing is needed: setup of a European program and report of the first joined regional quality assessment rounds

Ellen Bellon et al. Oncologist. 2011.

Abstract

The use of epidermal growth factor receptor-targeting antibodies in metastatic colorectal cancer has been restricted to patients with wild-type KRAS tumors by the European Medicines Agency since 2008, based on data showing a lack of efficacy and potential harm in patients with mutant KRAS tumors. In an effort to ensure optimal, uniform, and reliable community-based KRAS testing throughout Europe, a KRAS external quality assessment (EQA) scheme was set up. The first large assessment round included 59 laboratories from eight different European countries. For each country, one regional scheme organizer prepared and distributed the samples for the participants of their own country. The samples included unstained sections of 10 invasive colorectal carcinomas with known KRAS mutation status. The samples were centrally validated by one of two reference laboratories. The laboratories were allowed to use their own preferred method for histological evaluation, DNA isolation, and mutation analysis. In this study, we analyze the setup of the KRAS scheme. We analyzed the advantages and disadvantages of the regional scheme organization by analyzing the outcome of genotyping results, analysis of tumor percentage, and written reports. We conclude that only 70% of laboratories correctly identified the KRAS mutational status in all samples. Both the false-positive and false-negative results observed negatively affect patient care. Reports of the KRAS test results often lacked essential information. We aim to further expand this program to more laboratories to provide a robust estimate of the quality of KRAS testing in Europe, and provide the basis for remedial measures and harmonization.

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Conflict of interest statement

Disclosures

Ellen Bellon: None; Marjolijn J.L. Ligtenberg: None; Sabine Tejpar: Honoraria: Merck Serono; Research funding/contracted research: Pfizer, Merck Serono; Karen Cox: None; Gert de Hertogh: None; Karin de Stricker: None; Anders Edsjö: None; Vassilis Gorgoulis: None; Gerald Höfler: None; Andreas Jung: Consultant/advisory role: Amgen, Merck Serono; Honoraria: Merck Serono; Athanassios Kotsinas: None; Pierre Laurent-Puig: Consultant/advisory role: Merck Serono; Research funding/contracted research: Merck Serono; Fernando López-Ríos: None; Tine Plato Hansen: None; Etienne Rouleau: Consultant/advisory role: Fluigent; Research funding/contracted research: Amgen; Peter Vandenberghe: None; Johan J.M. van Krieken: None; Elisabeth Dequeker: None.

Section Editor Richard Goldberg discloses a consulting relationship with Amgen, Bayer, Genentech, Genomic Health, Lilly, and sanofi-aventis; and research funding from Amgen, Bayer, Genentech, sanofi-aventis, and Enzon.

Section Editor Patrick Johnston discloses employment with Almac Diagnostics; intellectual property including 12 patents; a consulting relationship with Almac, Roche, Chugai Pharmaceuticals, and sanofi-aventis; honoraria received from AstraZeneca, Chugai Pharmaceuticals, Pfizer, sanofi-aventis, Roche, and ASCO; research funding from AstraZeneca and Amgen; and ownership interests in Almac Diagnostics and Fusion Antibodies.

Section Editor Peter O'Dwyer discloses a consulting relationship with Tetralogic Pharmaceuticals, PrECOG, and AstraZeneca; an advisory relationship with Nereus Pharmaceutical, Tetralogic Pharmaceuticals, and PrECOG; research support from Pfizer, Bristol-Myers Squibb, Methylgene, Novartis, Genentech, Bayer, Merck, Kosan, Ardea, and Exelixis; honoraria received from Genentech, Bayer, Methylgene, and Bristol-Myers Squibb; and ownership interest with Tetralogic Pharmaceuticals.

Reviewer “A” discloses no financial relationships.

The content of this article has been reviewed by independent peer reviewers to ensure that it is balanced, objective, and free from commercial bias. On the basis of disclosed information, all conflicts of interest have been resolved.

Figures

Figure 1.
Figure 1.
Schematic representation of the preparation and distribution of the samples in the KRAS external quality assessment scheme. (1) represents the first validation of the samples by the scheme organizer before sending the samples. (2) represents the second, central validation of the samples by the reference laboratory. (3) represents the analysis of the samples by the participating laboratories.
Figure 2.
Figure 2.
Results of tumor percentages in the different samples of the KRAS external quality assessment scheme.
Figure 3.
Figure 3.
Scores of different items of the reports of the KRAS external quality assessment scheme, according to the ISO 15189:2007 standard and Gulley et al. (2007) [14]. n = 53 reports analyzed.
See this image and copyright information in PMC

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