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经支气管镜活检小量标本检测EGFR突变基因在晚期肺腺癌患者中的应用
聂云强1,李翠云1,李娜1,张晓艳2,王辉1,郭大彩1,韩平1,吕欣1,刘淑玲1,王长岭1,许新毅1*
0
(1. 临沂市人民医院呼吸内科, 临沂 276003;
2. 临沂市人民医院肿瘤科, 临沂 276003
*通信作者)
摘要:
目的 经支气管镜活检小量标本检测表皮生长因子受体(epidermal growth factor receptor, EGFR)基因突变,指导临床靶向治疗.方法 ⅢB~Ⅳ期女性肺腺癌患者56例,行内镜下气管腔内瘤组织活检或经支气管针吸活检术活检纵隔、肺门淋巴结,共收集标本64例,其中内镜下支气管内单纯组织活检标本20例,单纯淋巴结穿刺活检标本(TBNA)28例,支气管腔内组织及纵隔、肺门淋巴结均活检的标本8例.明确诊断肺腺癌后行EGFR基因检测,分别检测19、21外显子突变,将标本分为支气管腔内转移组和淋巴结转移组,统计分析两组外显子突变情况及患者靶向治疗临床疗效.结果 19外显子突变在支气管腔内转移组阳性率较高(χ2=4.304,P=0.038),21外显子突变在在淋巴结转移组阳性率较高(χ2=18.727,P=0.000).共24例纳入临床疗效评估,其中支气管腔内转移患者10例(19外显子突变8例,21外显子突变2例),疾病控制率90%(9/10),中位无进展生存期14.8个月;淋巴结转移患者14例(19外显子突变3例,21外显子突变11例),疾病控制率78.57%(11/14),中位无进展生存期9.2个月,两组疾病控制率差异无统计学意义(P>0.05),中位无进展生存期差异有统计学意义(χ2=4.134, P=0.042).结论 女性晚期肺腺癌EGFR外显子突变与不同转移形式有一定的关系,19外显子突变易出现于支气管内转移,21外显子突变易出现于淋巴结转移;支气管内转移的患者靶向治疗效果好于淋巴结转移的患者.
关键词:  肺肿瘤  腺癌  表皮生长因子受体  突变  酪氨酸激酶抑制剂  活组织检查  支气管镜检查
DOI:10.3724/SP.J.1008.2015.00049
投稿时间:2014-03-09修订日期:2014-11-01
基金项目:临沂市科技发展计划项目(201313006).
Small bronchoscopic biopsy specimens for detecting EGFR gene mutations in advanced lung adenocarcinoma
NIE Yun-qiang1,LI Cui-yun1,LI Na1,ZHANG Xiao-yan2,WANG Hui1,GUO Da-cai1,HAN Ping1,LÜ Xin1,LIU Shu-ling1,WANG Chang-ling1,XU Xin-yi1*
(1. Department of Respiratory Medicine, People's Hospital of Linyi, Linyi 276003, Shandong, China;
2. Department of Oncology, People's Hospital of Linyi, Linyi 276003, Shandong, China
*Corresponding author)
Abstract:
Objective To examine epidermal growth factor receptor (EGFR) gene mutations in small bronchoscopic biopsy specimens, so as to provide guidance for clinical targeted therapy. Methods Fifty-six female patients with advanced-stage ⅢB-Ⅳ lung adenocarcinoma underwent endoscopic endobronchial biopsy of tumor tissues or transbronchial needle aspiration of mediastinal and hilar lymph nodes. Under the endoscope, 20 patients underwent only bronchial biopsy, 28 underwent only transbronchial needle aspiration (TBNA) lymph node biopsy, and 8 underwent both endobronchial biopsy and TBNA biopsy of mediastinal and hilar lymph nodes. A total of 64 specimens were collected and were subjected to detection of EGFR gene mutations after confirmation of lung adenocarcinoma. The specimens were then divided into endobronchial metastasis group and lymph node metastasis group, and the mutations of exons 19 and 21 were detected and the clinical efficacy of targeted therapy was analyzed. Results Exon 19 had higher positive rate in the endobronchial metastasis group (χ2=4.304,P=0.038), and exon 21 had higher positive rate in lymph node metastasis group (χ2=18.727,P=0.000). A total of 24 cases were included for the clinical efficacy assessments: 10 had endobronchial metastasis (exon 19 mutations in 8 cases, 21 exon in 2 cases), with the disease control rate being 90% (9/10) and median progression-free survival period being 14.8 months; 14 patients had lymph node metastasis (19 exon 3 cases, 21 exon 11 cases), with the disease control rate being 78.57% (11/14) and the median progression-free survival period being 9.2 months; the disease control rates were not significantly different between the two groups (P>0.05) and the median progression-free survival periods were significantly different between the two groups(χ2 = 4.134, P=0.042). Conclusion Mutations of different EGFR exons might relate to the metastasis forms of female advanced lung adenocarcinoma, with exon 19 prone to endobronchial metastasis and exon 21 to lymph node metastasis. Targeted therapy for patients with endobronchial metastasis has a better outcome than that for patients with lymph node metastasis.
Key words:  lung neoplasms  adenocarcinoma  epidermal growth factor receptor  mutation  tyrosine kinase inhibitors  biopsy  bronchoscopy