Department of Respiratory Diseases, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Peking University, Beijing, China.
Respiration. 2013;85(2):119-25. doi: 10.1159/000338790. Epub 2012 Jul 10.
Epidermal growth factor receptor (EGFR) mutations play essential roles in the treatment of non-small cell lung cancer (NSCLC) patients using EGFR tyrosine kinase inhibitors. Detection of EGFR mutations in blood cell-free DNA (cfDNA) seems promising. However, the mutation status in the plasma/serum is not always consistent with that in the tissues.
The aims of this study were to compare the mutation statuses in plasma to those in tissues and thus to determine the specific subgroups of NSCLC patients who may be the best candidates for EGFR mutation analyses using blood cfDNA.
A total of 111 pairs of tissue and plasma samples were collected. Mutant-enriched PCR and sequencing analyses were performed to detect EGFR exon 19 deletions and exon 21 L858R mutations.
Mutations were discovered in 43.2% (48/111) of the patients. The overall rate of consistency of the EGFR mutation statuses for the 111 paired plasma and tissue samples was 71.2% (79/111). The sensitivity and specificity rates of detecting EGFR mutations in the plasma were 35.6% (16/45) and 95.5% (63/66), respectively. The disease stage and tumor differentiation subgroups showed significantly different detection sensitivities; the sensitivity was 10% in early-stage patients and 56% in advanced-stage patients (p = 0.0014). For patients with poorly differentiated tumors, the sensitivity was 77.8%, which was significantly different from those with highly differentiated (20%; p = 0.0230) and moderately differentiated tumors (19%; p = 0.0042).
Blood analyses for EGFR mutations may be effectively used in advanced-stage patients or patients with poorly differentiated tumors.
表皮生长因子受体 (EGFR) 突变在使用 EGFR 酪氨酸激酶抑制剂治疗非小细胞肺癌 (NSCLC) 患者中发挥着重要作用。检测血液游离 DNA (cfDNA) 中的 EGFR 突变似乎很有前景。然而，血浆/血清中的突变状态并不总是与组织中的突变状态一致。
本研究旨在比较血浆和组织中的突变状态，从而确定最适合使用血液 cfDNA 进行 EGFR 突变分析的 NSCLC 患者的具体亚组。
共收集了 111 对组织和血浆样本。采用突变富集 PCR 和测序分析方法检测 EGFR 外显子 19 缺失和外显子 21 L858R 突变。
43.2%（48/111）的患者发现存在突变。111 对血浆和组织样本的 EGFR 突变状态总体一致性率为 71.2%（79/111）。检测血浆中 EGFR 突变的灵敏度和特异性分别为 35.6%（16/45）和 95.5%（63/66）。疾病分期和肿瘤分化亚组的检测灵敏度存在显著差异；早期患者的灵敏度为 10%，晚期患者的灵敏度为 56%（p=0.0014）。对于分化差的肿瘤患者，灵敏度为 77.8%，与高分化（20%；p=0.0230）和中分化肿瘤（19%；p=0.0042）患者的灵敏度有显著差异。
血液 EGFR 突变分析可能在晚期患者或分化差的肿瘤患者中有效使用。
