Department of Thoracic Surgery, Kitasato University School of Medicine, 1-15-1 Kitasato, Minami-Ku, Sagamihara, Kanagawa, 252-0374, Japan.
Department of Pathology, Kitasato University Hospital, Sagamihara, Japan.
Virchows Arch. 2021 Mar;478(3):507-516. doi: 10.1007/s00428-020-02919-0. Epub 2020 Aug 31.
Liquid-based cytology (LBC) specimens of lung adenocarcinoma have the potential to be widely used for genetic analysis. However, formaldehyde contained in some LBC preservation solutions can cause DNA fragmentation during specimen storage, rendering the samples unsuitable for molecular analysis. To investigate a novel preservation technique for improved DNA stability, which was evaluated by mutation analysis of epidermal growth factor receptor (EGFR) gene in human lung adenocarcinoma cell lines. Cells were fixed in CytoRich Red preservation solution. After 30 min of fixation, cells were either stored using the conventional method (suspended in preservation solution) or washed in phosphate-buffered saline and stored as a cell pellet (newly proposed method). The effect of storage was evaluated after 5, 7, and 9 days of storage at ambient temperature. The cell pellet group was also tested after 14 and 28 days. Specifically, we evaluated the DNA stability, DNA yield, and sample suitability for polymerase chain reaction (PCR), and EGFR mutation detection. The DNA yields and degree of stability from the cell pellet group were higher than those from the suspension group at every time point examined. PCR amplification from the cell pellet group was successful up to day 28. Mutation detection using the Cycleave PCR method indicated that the Ct values of the cell pellet group were significantly lower than those of the suspension group. Storing LBC specimens as a cell pellet post-fixation can maintain the DNA quality for a longer period than the conventional method, making it a promising strategy for molecular analysis.
液体基细胞学(LBC)标本的肺腺癌有可能被广泛用于遗传分析。然而,一些 LBC 保存液中含有的甲醛会在标本储存过程中导致 DNA 片段化,使样本不适合进行分子分析。为了研究一种新的保存技术以提高 DNA 的稳定性,我们评估了其对人肺腺癌细胞系表皮生长因子受体(EGFR)基因突变分析的影响。细胞用 CytoRich Red 保存液固定。固定 30 分钟后,细胞要么采用传统方法(悬浮在保存液中)保存,要么用磷酸盐缓冲盐水洗涤后作为细胞沉淀保存(新提出的方法)。在室温下储存 5、7 和 9 天后评估储存效果。细胞沉淀组也在 14 和 28 天后进行了测试。具体来说,我们评估了 DNA 的稳定性、DNA 产量以及用于聚合酶链反应(PCR)和 EGFR 突变检测的样本适用性。在每个检测时间点,细胞沉淀组的 DNA 产量和稳定性均高于悬浮组。细胞沉淀组的 PCR 扩增可成功进行至第 28 天。使用 Cycleave PCR 方法进行突变检测表明,细胞沉淀组的 Ct 值明显低于悬浮组。与传统方法相比,固定后将 LBC 标本作为细胞沉淀储存可以更长时间地保持 DNA 质量,是一种很有前途的分子分析策略。