Dejima Hitoshi, Nakanishi Hayao, Takeyama Ryo, Nishida Tomoki, Yamauchi Yoshikane, Saito Yuichi, Sakao Yukinori
Department of Surgery, Teikyo University School of Medicine, Itabashi-ku, Tokyo 1738605, Japan.
Department of General Thoracic Surgery, Shin-Kuki General Hospital, Kuki 3468530, Japan.
Diagnostics (Basel). 2024 Sep 18;14(18):2064. doi: 10.3390/diagnostics14182064.
Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors are powerful molecular targeted therapeutic agents for lung cancer. We recently developed an original immunocytology and glass slide-based circulating tumor cell (CTC) detection platform for both CTC enumeration and EGFR mutation analysis with DNA extracted from CTCs.
Using this platform, we conducted a pilot clinical study for CTC enumeration in peripheral blood (PB), pulmonary arterial blood (PA), and pulmonary venous blood (PV) from 33 patients with lung cancer (Stage I-III) who underwent surgery, followed by digital PCR-based EGFR mutation analysis of CTCs in PV from 12 patients.
The results showed that CTC levels were significantly higher in PV and PA than in PB ( < 0.05, < 0.01. respectively), with a notably greater number of small and large CTC clusters ( < 0.01). Genetic analysis of EGFR mutations of CTCs from PV ( = 12) revealed six mutations, including three Exon19del and three L856R, in CTCs and eight EGFR mutations, including five Exon19del and three L856R, in lung tumor tissue. CTC mutation status matched that of tissue samples in nine patients, was unmatched in two patients, and controversial in one patient, indicating a sensitivity of 0.75 (6/8) and specificity of 1.0 (4/4) with some false-negative results for the mutation analysis of CTCs.
This immunocytology-based CTC detection platform is a convenient method for detecting both CTC number and EGFR mutation status under microscopy, suggesting its potential as a liquid biopsy tool in the hospital for patients with lung cancer in some clinical settings.
表皮生长因子受体（EGFR）酪氨酸激酶抑制剂是治疗肺癌的强效分子靶向治疗药物。我们最近开发了一种基于免疫细胞学和玻片的循环肿瘤细胞（CTC）检测平台，用于从CTC中提取DNA进行CTC计数和EGFR突变分析。
使用该平台，我们对33例接受手术的肺癌患者（I - III期）的外周血（PB）、肺动脉血（PA）和肺静脉血（PV）进行了CTC计数的初步临床研究，随后对12例患者PV中的CTC进行了基于数字PCR的EGFR突变分析。
结果显示，PV和PA中的CTC水平显著高于PB（分别为P<0.05，P<0.01），小和大的CTC簇数量明显更多（P<0.01）。对来自PV（n = 12）的CTC进行EGFR突变基因分析发现，CTC中有6个突变，包括3个Exon19del和3个L856R，肺肿瘤组织中有8个EGFR突变，包括5个Exon19del和3个L856R。9例患者的CTC突变状态与组织样本匹配，2例患者不匹配，1例患者存在争议，表明CTC突变分析的敏感性为0.75（6/8），特异性为1.0（4/4），有一些假阴性结果。
这种基于免疫细胞学的CTC检测平台是一种在显微镜下检测CTC数量和EGFR突变状态的便捷方法，表明其在某些临床环境中作为肺癌患者医院液体活检工具的潜力。
