Lehmann Annika, Schewe Christiane, Hennig Guido, Denkert Carsten, Weichert Wilko, Budczies Jan, Dietel Manfred
Institute of Pathology, Charité University Hospital, Berlin, Germany.
Diagn Mol Pathol. 2012 Jun;21(2):114-9. doi: 10.1097/PDM.0b013e31823569ca.
Due to the approval of various new targeted therapies for the treatment of cancer, molecular pathology laboratories with a diagnostic focus have to meet new challenges: simultaneous handling of a large number of samples, small amounts of input material, and fragmentation of nucleic acids because of formalin fixation. As a consequence, fully automated systems for a fast and standardized extraction of high-quality DNA from formalin-fixed paraffin-embedded (FFPE) tissues are urgently needed. In this study, we tested the performance of a fully automated, high-throughput method for the extraction of nucleic acids from FFPE tissues. We investigated the extraction performance in sections of 5 different tissue types often analyzed in routine pathology laboratories (cervix, colon, liver, lymph node, and lung; n=340). Furthermore, we compared the quality, labor input, and applicability of the method for diagnostic purposes with those of a laboratory-validated manual method in a clinical setting by screening a set of 45 colorectal adenocarcinoma for the KRAS mutation. Automated extraction of both DNA and RNA was successful in 339 of 340 FFPE samples representing 5 different tissue types. In comparison with a conventional manual extraction protocol, the method showed an overall agreement of 97.7% (95% confidence interval, 88.2%-99.9%) for the subsequent mutational analysis of the KRAS gene in colorectal cancer samples. The fully automated system is a promising tool for a simple, robust, and rapid extraction of DNA and RNA from formalin-fixed tissue. It ensures a standardization of sample processing and can be applied to clinical FFPE samples in routine pathology.
由于多种用于癌症治疗的新型靶向疗法获得批准,专注于诊断的分子病理学实验室不得不应对新的挑战:同时处理大量样本、少量输入材料以及因福尔马林固定导致的核酸片段化。因此,迫切需要一种能够从福尔马林固定石蜡包埋(FFPE)组织中快速、标准化地提取高质量DNA的全自动系统。在本研究中,我们测试了一种从FFPE组织中提取核酸的全自动高通量方法的性能。我们研究了在常规病理实验室中经常分析的5种不同组织类型(宫颈、结肠、肝脏、淋巴结和肺;n = 340)切片中的提取性能。此外,我们通过筛查一组45例结肠直肠癌样本中的KRAS突变,在临床环境中将该方法用于诊断目的的质量、人力投入和适用性与实验室验证的手动方法进行了比较。在代表5种不同组织类型的340个FFPE样本中,有339个成功实现了DNA和RNA的自动提取。与传统的手动提取方案相比,该方法在结肠直肠癌样本中KRAS基因的后续突变分析中总体一致性为97.7%(95%置信区间,88.2% - 99.9%)。该全自动系统是一种从福尔马林固定组织中简单、稳健且快速提取DNA和RNA的有前景的工具。它确保了样本处理的标准化,并且可应用于常规病理学中的临床FFPE样本。