Kang Hyo Jae, Hwangbo Bin, Lee Jin Soo, Kim Moon Soo, Lee Jong Mog, Lee Geon-Kook
Center for Lung Cancer, Research Institute and Hospital, National Cancer Center, Goyang, Korea.
Department of Pathology, Research Institute and Hospital, National Cancer Center, Goyang, Korea.
PLoS One. 2016 Sep 29;11(9):e0163652. doi: 10.1371/journal.pone.0163652. eCollection 2016.
Although the use of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is increasing for epidermal growth factor receptor (EGFR) testing in lung cancer, the discordance rate in EGFR mutations between lymph node (LN) samples obtained by EBUS-TBNA and primary tumor (PT) is not well known. Thus, we compared the EGFR mutation status of LN samples obtained by EBUS-TBNA and PTs to estimate the efficacy of using EBUS-TBNA specimens for EGFR testing in advanced, non-squamous, non-small cell lung cancer (NSCLC).
Using data of patients from the EBUS-TBNA database (N = 1914) obtained between January 2009 and January 2013, we identified 100 treatment-naïve, advanced, non-squamous NSCLC patients (stage 3 and 4) with matched LN specimens obtained by EBUS-TBNA and PT specimens. Of these, 74 patients with paired specimens were feasible for EGFR mutation analysis, which we performed using a direct sequencing method.
Of the 74 cases, at least one major [exon 19 deleted (19del) and L858R] or minor (T790M, exon 20 insertion, and other point mutations) EGFR mutation was detected in 31 cases (41.9%), which included PT (n = 31, 41.9%) and LN (n = 28, 37.8%) specimens. Major mutations were detected in 25 PT (33.8%, 19del = 13, L858R = 12) and 22 LN (29.8%, 19del = 11, L858R = 11) specimens. The discordance rate in major mutations between matched PT and LN specimens was 4.1% (3/74). Among minor mutations, T790M was detected in LN specimen only in 2 cases with L858R in PT and LN. The discordance rate major and minor EGFR mutations combined between matched PT and LN specimens was 12% (9/74).
We observed a high concordance rate of major EGFR mutations between matched LN specimens sampled by EBUS-TBNA and PTs, suggesting that LN samples obtained by EBUS-TBNA from advanced non-squamous NSCLC patients are effective for use in EGFR mutation testing.
尽管支气管内超声引导下经支气管针吸活检术（EBUS-TBNA）在肺癌表皮生长因子受体（EGFR）检测中的应用日益增多，但EBUS-TBNA获取的淋巴结（LN）样本与原发性肿瘤（PT）之间EGFR突变的不一致率尚不清楚。因此，我们比较了EBUS-TBNA获取的LN样本和PT的EGFR突变状态，以评估在晚期非鳞状非小细胞肺癌（NSCLC）中使用EBUS-TBNA标本进行EGFR检测的有效性。
利用2009年1月至2013年1月期间从EBUS-TBNA数据库获取的患者数据（N = 1914），我们确定了100例未经治疗的晚期非鳞状NSCLC患者（3期和4期），他们同时有通过EBUS-TBNA获取的匹配LN标本和PT标本。其中，74例有配对标本的患者可行EGFR突变分析，我们采用直接测序法进行检测。
在这74例病例中，31例（41.9%）检测到至少一种主要（外显子19缺失[19del]和L85 8R）或次要（T790M、外显子20插入和其他点突变）EGFR突变，包括PT标本（n = 31，41.9%）和LN标本（n = 28，37.8%）。25例PT标本（33.8%，19del = 13，L858R = 12）和22例LN标本（29.8%，19del = 11，L858R = 11）检测到主要突变。匹配的PT和LN标本之间主要突变的不一致率为4.1%（3/74）。在次要突变中，仅在2例PT和LN中存在L858R的LN标本中检测到T790M。匹配的PT和LN标本之间主要和次要EGFR突变合并后的不一致率为12%（9/74）。
我们观察到EBUS-TBNA采集的匹配LN标本与PT之间主要EGFR突变的一致性率较高，这表明从晚期非鳞状NSCLC患者中通过EBUS-TBNA获取的LN样本可有效用于EGFR突变检测。
