Department of Pathology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India.
Department of Pathology & Lab Medicine, AIIMS Raebareli, Raebareli, Uttar Pradesh, India.
Asian Pac J Cancer Prev. 2023 Oct 1;24(10):3467-3475. doi: 10.31557/APJCP.2023.24.10.3467.
Testing for EGFR, ALK, ROS1 and MET alterations in paired tissue and plasma samples of treatment-naïve patients of NSCLC and correlating their status with overall survival.
One hundred treatment-naïve patients were recruited after obtaining informed consent. Ten ml of blood was collected within a period of two weeks from histological diagnosis, prior to the start of any treatment. DNA & RNA extraction was done from formalin-fixed paraffin embedded (FFPE) tissue and total cell-free nucleic acid extraction was done from plasma samples. EGFR mutation, ALK, ROS1 and MET rearrangements were tested by ARMS (Amplification Refractory Mutation System) PCR. All statistical analyses were conducted in R version 4.1.1.
A total of 61 cases showed molecular alterations in tissue samples which included EGFR mutations (47), ALK rearrangements (12), ROS1 fusion (2). MET alteration was not detected. Forty-three cases showed EGFR mutations in plasma, 26 of which were concurrently positive in tissue. Concordance observed was 62%. ALK-EML4 rearrangement, ROS1 fusion and MET were not detected in plasma samples. Sensitivity and specificity for detection of EGFR mutation in plasma were 55.3% and 67.9% respectively. Univariate Cox regression analysis showed a positive association between EGFR mutation in tissue and overall survival (HR = 0.4; 95% CI: 0.2-0.7; p = 0.003) and improved overall survival in those who received targeted therapy (HR = 0.29; 95% CI: 0.1-0.8; p = 0.02).
Concurrent testing in tissue and liquid biopsy in NSCLC increased the detection of EGFR mutations (47% to 64%). This has substantial implications in deciding treatment and administration targeted therapy and the consequent overall survival.
检测未经治疗的 NSCLC 患者配对组织和血浆样本中的 EGFR、ALK、ROS1 和 MET 改变，并将其与总生存期相关联。
获得知情同意后，招募了 100 名未经治疗的患者。在开始任何治疗之前的两周内，从组织学诊断中采集 10 毫升血液。从福尔马林固定石蜡包埋（FFPE）组织中提取 DNA 和 RNA，并从血浆样本中提取总游离核酸。通过 ARMS（扩增受阻突变系统）PCR 检测 EGFR 突变、ALK、ROS1 和 MET 重排。所有统计分析均在 R 版本 4.1.1 中进行。
共有 61 例组织样本显示分子改变，包括 EGFR 突变（47 例）、ALK 重排（12 例）、ROS1 融合（2 例）。未检测到 MET 改变。43 例血浆中显示 EGFR 突变，其中 26 例在组织中同时阳性。一致性观察为 62%。ALK-EML4 重排、ROS1 融合和 MET 未在血浆样本中检测到。血浆中 EGFR 突变的检测灵敏度和特异性分别为 55.3%和 67.9%。单因素 Cox 回归分析显示，组织中 EGFR 突变与总生存期呈正相关（HR=0.4；95%CI：0.2-0.7；p=0.003），并改善了接受靶向治疗患者的总生存期（HR=0.29；95%CI：0.1-0.8；p=0.02）。
在 NSCLC 中同时检测组织和液体活检增加了 EGFR 突变的检测率（从 47%增加到 64%）。这对决定治疗方案和实施靶向治疗以及随后的总生存期具有重要意义。
