Kang Yeh Rim, Park Hye Yun, Jeon Kyeongman, Koh Won-Jung, Suh Gee Young, Chung Man Pyo, Kim Hojoong, Kwon O Jung, Choi Yoon-La, Han Joungho, Um Sang-Won
Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
Thorac Cancer. 2013 Aug;4(3):264-272. doi: 10.1111/1759-7714.12006.
Procurement of tumor tissue is mandatory for a mutation analysis in patients with non-small cell lung cancer. The purpose of this study was to evaluate the usefulness of bronchoscopic biopsy and endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) biopsy for detecting epidermal growth factor receptor (EGFR) and KRAS mutations in routine practice.
Tumor DNA was extracted from formalin-fixed paraffin-embedded tissues, and amplifications of exons 18-21 of EGFR and codons 12, 13 and 61 of KRAS were performed using polymerase chain reaction (PCR). PCR products were subjected to direct sequencing in both directions.
Of 211 consecutive specimens, 201 (95.3%) were available for EGFR mutation analysis, and 196 (92.9%) were adequate for KRAS mutation analysis. EGFR and KRAS mutations were detected in 14.9% and 5.4%, respectively. A median of 16 days was spent from biopsy to the final report for either EGFR or KRAS mutation status. The detection rates for both mutations were similar between bronchoscopic biopsy and EBUS-TBNA (P > 0.05). Female gender (53.3%), never smoker (63.3%), and adenocarcinoma (96.7%) were predominant in patients with EGFR mutations. Among patients with adenocarcinoma (n = 104), the frequencies of EGFR and KRAS mutations were 27.9% and 10.6%, respectively.
Small tissue samples obtained by bronchoscopic biopsy and EBUS-TBNA are sufficient for detecting EGFR and KRAS mutations in routine practice. Therefore, concurrent mutational analyses of small tissue samples should be considered at the time of initial diagnosis.
对于非小细胞肺癌患者,获取肿瘤组织进行突变分析是必要的。本研究的目的是评估在常规实践中,支气管镜活检和支气管内超声引导下经支气管针吸活检(EBUS-TBNA)对检测表皮生长因子受体(EGFR)和KRAS突变的有效性。
从福尔马林固定石蜡包埋组织中提取肿瘤DNA,使用聚合酶链反应(PCR)对EGFR的18-21外显子和KRAS的12、13和61密码子进行扩增。PCR产物进行双向直接测序。
在211个连续标本中,201个(95.3%)可用于EGFR突变分析,196个(92.9%)可用于KRAS突变分析。EGFR和KRAS突变的检测率分别为14.9%和5.4%。从活检到最终报告EGFR或KRAS突变状态的中位时间为16天。支气管镜活检和EBUS-TBNA对两种突变的检测率相似(P>0.05)。EGFR突变患者中女性(53.3%)、从不吸烟者(63.3%)和腺癌(96.7%)占主导。在腺癌患者(n=104)中,EGFR和KRAS突变的频率分别为27.9%和10.6%。
在常规实践中,通过支气管镜活检和EBUS-TBNA获得的小组织样本足以检测EGFR和KRAS突变。因此,在初始诊断时应考虑对小组织样本进行同步突变分析。