Tack Véronique, Ligtenberg Marjolijn J L, Tembuyser Lien, Normanno Nicola, Vander Borght Sara, Han van Krieken J, Dequeker Elisabeth M C
Biomedical Quality Assurance Research Unit, Department of Public Health and Primary Care, KU Leuven, Leuven, Belgium; Department of Pathology, Radboud University Medical Center, Nijmegen, The Netherlands; Cell Biology and Biotherapy Unit, Istituto Nazionale per lo Studio e la Cura dei Tumori "Fondazione Giovanni Pascale" - IRCCS, Naples, Italy; Department of Pathology, UZ Leuven, Leuven, Belgium.
Biomedical Quality Assurance Research Unit, Department of Public Health and Primary Care, KU Leuven, Leuven, Belgium; Department of Pathology, Radboud University Medical Center, Nijmegen, The Netherlands; Cell Biology and Biotherapy Unit, Istituto Nazionale per lo Studio e la Cura dei Tumori "Fondazione Giovanni Pascale" - IRCCS, Naples, Italy; Department of Pathology, UZ Leuven, Leuven, Belgium
Oncologist. 2015 Mar;20(3):257-62. doi: 10.1634/theoncologist.2014-0382. Epub 2015 Feb 5.
Regulations for the selection of patients with metastatic colorectal cancer for anti-EGFR treatment changed at the end of 2013. The set of mutations to be tested extended from KRAS codons 12 and 13 to KRAS and NRAS exons 2, 3, and 4. A European external quality assessment scheme monitored the performance of laboratories and evaluated the implementation of the new regulations.
The 131 participating laboratories received 10 samples of formalin-fixed paraffin-embedded material, including RAS (exon 2, 3, 4) and BRAF mutations. Mock clinical data were provided for three cases. Using their routine methods, laboratories determined the genotypes and submitted three written reports. Assessors scored the results according to predefined evaluation criteria.
Half of the participants (49.3%) had completely implemented the new test requirements (codons 12, 13, 59, 61, 117, and 146 of KRAS and NRAS), and 96 laboratories (73.3%) made no genotype mistakes. Correct nomenclature, according to the Human Genome Variation Society, was used by 82 laboratories (62.6%).
Although regulations were effective for several months, many laboratories were not ready for full RAS testing in the context of anti-EGFR therapy. Nevertheless, in each participating country, there are laboratories that provide complete and correct testing. External quality assessments can be used to monitor implementation of new test regulations and to stimulate the laboratories to improve their testing procedures. Because the results of this program are available on the website of the European Society of Pathology, patients and clinicians can refer test samples to a reliable laboratory.
2013年底，转移性结直肠癌患者抗表皮生长因子受体（EGFR）治疗的患者选择标准发生了变化。需检测的突变组从KRAS基因第12和13密码子扩展到KRAS和NRAS基因的第2、3和4外显子。一项欧洲外部质量评估计划监测了各实验室的表现，并评估了新规定的实施情况。
131家参与实验室收到了10份福尔马林固定石蜡包埋材料样本，包括RAS（第2、3、4外显子）和BRAF突变。为3例病例提供了模拟临床数据。实验室使用其常规方法确定基因型并提交3份书面报告。评估人员根据预先定义的评估标准对结果进行评分。
一半的参与者（49.3%）完全实施了新的检测要求（KRAS和NRAS基因的第12、13、59、61、117和146密码子），96家实验室（73.3%）没有出现基因型错误。82家实验室（62.6%）使用了符合人类基因组变异协会规定的正确命名法。
尽管相关规定已实施数月，但许多实验室尚未准备好在抗EGFR治疗背景下进行全面的RAS检测。然而，在每个参与国家，都有能够提供完整且正确检测的实验室。外部质量评估可用于监测新检测规定的实施情况，并促使实验室改进其检测程序。由于该计划的结果可在欧洲病理学会网站上获取，患者和临床医生可以将检测样本送检至可靠的实验室。
