Morikawa Kei, Kida Hirotaka, Handa Hiroshi, Inoue Takeo, Saji Hisashi, Koike Junki, Nakamura Seiji, Sato Yoshiharu, Ueda Yumi, Suzuki Fumihiko, Matoba Ryo, Mineshita Masamichi
Division of Respiratory Diseases, Department of Internal Medicine, St. Marianna University School of Medicine, Kawasaki 216-8513, Japan.
Department of Chest Surgery, St. Marianna University School of Medicine, Kawasaki 216-8513, Japan.
Cancers (Basel). 2022 Aug 3;14(15):3784. doi: 10.3390/cancers14153784.
Genetic panel tests require sufficient tissue samples, and therefore, cannot always be performed. Although collecting cytological specimens is easier than tissue collection, there are no validation studies on the diagnostic accuracy of lung cancer gene panel tests using cytology samples. Using an amplicon-based high-sensitivity next-generation sequencing panel test capable of measuring eight druggable genes, we prospectively enrolled consecutive patients who underwent diagnostic procedures. We evaluated the analysis accuracy rate, nucleic acid yield, and the quality of cytological specimens under brushing, needle aspiration, and pleural effusion. We then compared these specimens with collected tissue samples. In 163 prospectively enrolled cases, nucleic acid extraction and analysis accuracy was 100% in cases diagnosed with adenocarcinoma. Gene mutations were found in 68.7% of cases with 99.5% (95% CI: 98.2-99.9) concordance to companion diagnostics. The median DNA/RNA yield and DNA/RNA integrity number were 475/321 ng and 7.9/5.7, respectively. The correlation coefficient of the gene allele ratio in 64 cases compared with tissue samples was 0.711. The success of gene analysis using cytological specimens was high, and the yield and quality of the extracted nucleic acid were sufficient for panel analysis. Moreover, the allele frequency of gene mutations in cytological specimens showed high correlations with tissue specimens.
基因检测panel需要足够的组织样本，因此并非总能进行检测。虽然采集细胞学标本比采集组织更容易，但目前尚无关于使用细胞学样本进行肺癌基因检测panel诊断准确性的验证研究。我们使用一种基于扩增子的高灵敏度下一代测序检测panel，能够检测8个可靶向治疗的基因，前瞻性地纳入了接受诊断性检查的连续患者。我们评估了刷检、针吸和胸腔积液细胞学标本的分析准确率、核酸产量和质量。然后将这些标本与采集的组织样本进行比较。在163例前瞻性纳入的病例中，腺癌诊断病例的核酸提取和分析准确率为100%。68.7%的病例发现基因突变，与伴随诊断的一致性为99.5%（95%CI：98.2-99.9）。DNA/RNA产量中位数和DNA/RNA完整性数值分别为475/321 ng和7.9/5.7。与组织样本相比，64例病例中基因等位基因比率的相关系数为0.711。使用细胞学标本进行基因分析的成功率很高，提取的核酸产量和质量足以进行检测panel分析。此外，细胞学标本中基因突变的等位基因频率与组织标本显示出高度相关性。
