Department of Public Health and Primary Care, Biomedical Quality Assurance Research Unit, University of Leuven, Kapucijnenvoer 35 blok d, 3000, Leuven, Belgium.
Department of Pathology, Radboud University Medical Center, Nijmegen, The Netherlands.
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.
在转移性结直肠癌 (mCRC) 患者接受 EGFR 靶向药物治疗之前，应确定 KRAS 和 NRAS 基因（外显子 2、3 和 4）的野生型状态。用于确定 RAS 状态的检测方法存在很大差异，最近引入了更敏感的检测方法。质量评估计划的数据表明存在大量错误率。本研究评估了在成功通过外部质量评估 (EQA) 的欧洲实验室中 RAS 检测的完整性和正确性。要求参与者发送最近十名接受 RAS 状态检测的 mCRC 患者的材料。要求提供分离的 DNA、带有用于宏观解剖的标记区域的苏木精和曙红染色组织载玻片以及随附的患者报告。请求在参考实验室中使用下一代测序方法重新评估样本。共有 31 个实验室发送了请求的材料 (n = 309)。尽管有针对抗 EGFR 治疗的规定，但有一个研究所没有进行完整的 RAS 检测。在有足够 DNA 可用的情况下，对 274 个样本进行了重新分析。在 KRAS 和 NRAS 的热点密码子中，总共获得了七个不一致的结果，其中五个导致对抗 EGFR 治疗效果的不同预测（2%；n = 274）。结果表明，肿瘤学家可以依赖于在 EQA 中表现良好的实验室的质量。肿瘤学家需要意识到，检测实验室成功参与了 EQA 计划。一些 EQA 提供商在其网站上列出了表现良好的实验室。
