Ma MeiLi, Shi ChunLei, Qian JiaLin, Teng JiaJun, Zhong Hua, Han BaoHui
Department of pulmonary, Shanghai Chest Hospital, Shanghai JiaoTong University, Shanghai 200030, China.
Department of pulmonary, Shanghai Chest Hospital, Shanghai JiaoTong University, Shanghai 200030, China.
Gene. 2016 Oct 10;591(1):58-64. doi: 10.1016/j.gene.2016.06.053. Epub 2016 Jun 28.
The aim of this study was to assess the effectiveness and accuracy of blood-based circulating-free tumor DNA on testing epidermal growth factor receptor (EGFR) gene mutations.
In total, 219 non-small cell lung cancer patients in stages III-IV were enrolled into this study. All patients had tissue samples and matched plasma DNA samples. EGFR gene mutations were detected by the Amplification Refractory Mutation System (ARMS). We compared the mutations in tumor tissue samples with matched plasma samples and determined the correlation between EGFR mutation status and clinical pathologic characteristics.
The overall concordance rate of EGFR mutation status between the 219 matched plasma and tissue samples was 82% (179/219). The sensitivity and specificity for the ARMS EGFR mutation test in the plasma compared with tumor tissue were 60% (54/90) and 97% (125/129), respectively. The positive predictive value was 93% (54/58) and the negative predictive value was 78% (125/161). The median overall survival was longer for those with EGFR mutations than for those without EGFR mutations both in tissue samples (23.98 vs. 12.16months; P<0.001) and in plasma (19.96 vs. 13.63months; P=0.009). For the 68 patients treated with EGFR- tyrosine kinase inhibitors (TKIs), the median progression-free survival (PFS) was significantly prolonged in the EGFR mutant group compared to the non-mutation group in tumor tissue samples (12.26months vs. 2.40months, P<0.001). In plasma samples, the PFS of the mutant group was longer than that of the non-mutant group. However, there was no significant difference between the two groups (10.88months vs. 9.89months, P=0.411).
The detection of EGFR mutations in plasma using ARMS is relatively sensitive and highly specific. However, EGFR mutation status tested by ARMS in plasma cannot replace a tumor tissue biopsy. Positive EGFR mutation results detected in plasma are fairly reliable, but negative results are hampered by a high rate of false negatives.
本研究旨在评估基于血液的循环游离肿瘤DNA检测表皮生长因子受体（EGFR）基因突变的有效性和准确性。
总共219例Ⅲ-Ⅳ期非小细胞肺癌患者纳入本研究。所有患者均有组织样本和匹配的血浆DNA样本。采用扩增阻滞突变系统（ARMS）检测EGFR基因突变。我们比较了肿瘤组织样本与匹配血浆样本中的突变情况，并确定了EGFR突变状态与临床病理特征之间的相关性。
219对匹配的血浆和组织样本中EGFR突变状态的总体一致率为82%（179/219）。与肿瘤组织相比，血浆中ARMS法检测EGFR突变的敏感性和特异性分别为60%（54/90）和97%（125/129）。阳性预测值为93%（54/58），阴性预测值为78%（125/161）。在组织样本（23.98对12.16个月；P<0.001）和血浆（19.96对13.63个月；P=0.009）中，EGFR突变患者的中位总生存期均长于无EGFR突变患者。对于68例接受EGFR酪氨酸激酶抑制剂（TKIs）治疗的患者，在肿瘤组织样本中，EGFR突变组的中位无进展生存期（PFS）较非突变组显著延长（12.26个月对2.40个月，P<0.001）。在血浆样本中，突变组的PFS长于非突变组。然而，两组之间无显著差异（10.88个月对9.89个月，P=0.411）。
采用ARMS法检测血浆中的EGFR突变相对敏感且特异性高。然而，血浆中ARMS法检测的EGFR突变状态不能替代肿瘤组织活检。血浆中检测到的EGFR突变阳性结果相当可靠，但阴性结果受假阴性率高的影响。
