肺腺癌患者新鲜细胞学标本EGFR基因突变检测及意义

doi:10.3969/j.issn.1004-616x.2018.01.013

癌变·畸变·突变 ›› 2018, Vol. 30 ›› Issue (1): 67-70.doi: 10.3969/j.issn.1004-616x.2018.01.013

肺腺癌患者新鲜细胞学标本EGFR基因突变检测及意义

郭晓, 王蕊, 吴娟, 纪晓坤, 王珩, 张艳, 马阳, 杜芸

河北医科大学第四医院癌检中心, 河北石家庄 050011

收稿日期:2017-02-21 修回日期:2017-12-19 出版日期:2018-01-30 发布日期:2018-01-30
通讯作者: 杜芸,E-mail:yydd40@126.com E-mail:yydd40@126.com
作者简介:郭晓,E-mail:335754696@qq.com。
基金资助:
河北省科技厅项目（14277782D）

Significance of EGFR gene mutation in fresh cytological specimens of lung adenocarcinoma

GUO Xiao, WANG Rui, WU Juan, JI Xiaokun, WANG Heng, ZHANG Yan, MA Yang, DU Yun

Cancer Detection Center of the Fourth Affiliated Hospital of Hebei Medical University, Shijiazhuang 050011, Hebei, China

Received:2017-02-21 Revised:2017-12-19 Online:2018-01-30 Published:2018-01-30

摘要/Abstract

摘要： 目的：研究采用新鲜细胞学标本检测肺腺癌患者表皮生长因子受体（EGFR）基因突变情况，用于辅助判断阳性患者服用酪氨酸激酶抑制剂（TKI）的预后。方法：收集河北医科大学第四医院癌检中心的肺腺癌患者淋巴结针吸标本和胸腔积液标本313例，经HE染色、免疫细胞化学染色后由两位细胞病理医师确诊为肺腺癌后，采用ARMS法进行EGFR基因外显子18~21突变的检测，观察突变情况；对比EGFR基因突变阳性患者采用口服TKI药物靶向治疗或化疗的客观有效率（ORR）和无进展生存期（PFS）。结果：313例标本中确诊为肺腺癌293例，其中288例提取DNA成功并得到检测，提取成功率为98.1%（288/293），检测出130例突变，突变率为45.1%。肺腺癌患者的EGFR突变主要发生在女性、不吸烟患者中，与年龄无明显相关。EGFR基因外显子18~21突变阳性患者靶向治疗组和化疗组之间的ORR差异有统计学意义（P < 0.01），靶向治疗组的疗效和生存期都优于化疗组。新鲜细胞学标本检测的EGFR基因突变结果以及所测阳性患者的预后与以往文献均一致。结论：新鲜细胞学标本检测的EGFR突变结果准确，可以作为肿瘤组织的代替标本。

关键词: 表皮生长因子受体, 基因突变, 非小细胞肺癌, 靶向治疗, 化疗

Abstract: OBJECTIVE: This paper aims to study the mutation of epidermal growth factor receptor (EGFR) gene in fresh cytological specimens from patients with lung adenocarcinoma,and to determine the prognosis of positive patients by tyrosine kinase inhibitor (TKI). METHODS: A total of 313 specimens from needle aspiration and pleural effusion were collected in the Cancer Detection Center of the Fourth Hospital of Hebei Medical University. After HE and immunocytochemistry stainings,the specimens were diagnosed as lung adenocarcinoma by two cytology pathologists. The mutation of 18-21 exon was detectied using ARMS to observe mutations situation. Then, the objective response rate (ORR) and the progression-free survival (PFS) between the targeted group and the chemotherapy group of patients were comparedith. RESULTS: Among 313 cases,293 cases of lung adenocarcinoma were diagnosed,and DNA specimens were extracted from 288 cases,the success rate was about 98.3%. 130 mutations were found and the rate was 45.1%. EGFR mutation of adenocarcinoma patients mainly occurred to females,nonsmokers,but had nothing to do with age. The ORR was statistically different between the targeted group with chemotherapy (P < 0.01),and PFS curve of targeted group was on chemotherapy group. The efficacy and the survival time of targeted group and targeted and chemotherapy group were superior to that of chemotherapy group. The results of the EGFR mutation and the prognosis of the tested positive patients in the fresh cytology samples were consistent with that from previous literatures. CONCLUSION: The results of the test were accurate,and fresh cytological specimens can be used as a replacement for tumor tissue specimens.

Key words: epidermal growth factor receptor, fresh cytology specimens, gene mutation, lung adenocarcinoma, targeted therapy, chemotherapy

中图分类号:

R730.5

郭晓, 王蕊, 吴娟, 纪晓坤, 王珩, 张艳, 马阳, 杜芸. 肺腺癌患者新鲜细胞学标本EGFR基因突变检测及意义[J]. 癌变·畸变·突变, 2018, 30(1): 67-70.

GUO Xiao, WANG Rui, WU Juan, JI Xiaokun, WANG Heng, ZHANG Yan, MA Yang, DU Yun. Significance of EGFR gene mutation in fresh cytological specimens of lung adenocarcinoma[J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2018, 30(1): 67-70.

参考文献

[1] 支修益,石远凯,于金明. 中国原发性肺癌诊疗规范(2015年版)[J]. 中华肿瘤杂志,2015,37(1):67-78.
[2] SHI S,SHI Y,TAYLOR C R. Antigen retrieval imunohisto chemistry:review and future prospects in research and diagnosis over two decades[J]. J Histochem Cytochem,2011,59(1):13-32.
[3] CAO F F,ZHANG L L,WANG S,et al. Comparison of EGFR TKIs and chemotherapy in the treatment of non-small cell lung cancer as a first-line therapy[J]. Chin J Lung Cancer,2015,18(3):146-154.
[4] SCHILL J H,HARRINGTON D,BELANI C P,et al. Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer[J]. N Engl J Med,2002,346(2):92-92.
[5] 卢红阳,蔡菊芬,毛伟敏,等. 非小细胞肺癌辅助靶向治疗研究进展[J]. 肿瘤学杂志,2014,20(1):64-67.
[6] 王明华,刘明亮. 突变非小细胞肺癌一线治疗新进展[J]. 国外医药抗生素分册,2013,34(6):252-256.
[7] 陈晓莉,段秀梅,赵恒飞,等. 分子靶向药物治疗非小细胞肺癌的策略[J]. 中国药房,2014,25(22):2080-2083.
[8] 王荣,石冬琴,谢华,等. 非小细胞肺癌中EGFR基因突变及靶向药物治疗研究进展[J]. 中国药理学通报,2013,29(1):22-26.
[9] 李榕,韩宝惠. EGFR基因突变检测在肺癌中的临床意义[J]. 临床肿瘤学杂志,2004,9(4):420-425.
[10] 肖越. ARMS法在检测晚期肺腺癌不同小标本中EGFR基因突变的比较[D]. 南昌:南昌大学医学院,2014.
[11] FRANCIS H,SOLOMON B. The current status of targeted therapy for non-small cell lung cancer[J]. Int Med J,2010,40(9):611-618.
[12] KASAKA T,YATABE Y,ENDOH H,et al. Mutations of the epidermal growth fator receptor gene in lung cancer:biological and clinical implications[J]. Cancer Res,2004,64(24):8919-8923.
[13] PAEZ J G,JANNE P A,LEE J C,et al. EGFR mutat ions in lung cancer:Correlation with clicical response to gefitinib therapy[J]. Science,2004,304(5676):1497-1500.
[14] YNCH T J,BELL D W,SORDELLA R,et al. Activating mutations in the epidermal growth factor receptor underlying respon siveness of non small cell lung cancer to gefitinib[J]. N Engl J Med,2004,350(21):2129-2139.
[15] MOKTS,WU Y L,THONGPTASER S,et al. Gefitinib or carboplatin-paclitaxel inpulmoary adenocarcinoma[J]. N Eng J Med,2009,361(10):947-957.
[16] MAEMONDO M,INOUE A,KOBAYASHI K,et al. Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR[J]. N Engl J Med,2010,362(25):2380-2388.
[17] MITSUDOMI T,MORITA S,YATABE Y,et al. Gefitinib versus cisplatin plusdocetaxel in patients with non-small-cell lung cancer harbouringmutations of the epidermal growth factor receptor:an open label,randomized phase 3 trial[J]. Lancet Oncol,2010,11(2):121-128.
[18] ZHOU C,WU Y L,CHEN G,et al. Erlotinib versus chemotherapy as first-line treatmer for patients with advanced EGFR mutation-positive non-small-cell lung cancer:a multicentre,open-label,randomized,phase 3 study[J]. Lancet Oncol,2011,12(8):735-742.

肺腺癌患者新鲜细胞学标本EGFR基因突变检测及意义

Significance of EGFR gene mutation in fresh cytological specimens of lung adenocarcinoma

PDF

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 15

编辑推荐

Metrics

本文评价

[1]	马亚南, 吴楠, 金焰. 肿瘤微环境与卵巢癌化疗耐药机制的研究进展[J]. 癌变·畸变·突变, 2021, 33(5): 393-395,400.
[2]	李蕊瑞, 张立实, 陈锦瑶. 人群PIG-A基因突变测定的研究进展[J]. 癌变·畸变·突变, 2021, 33(5): 396-400.
[3]	刘晓霞, 李卫霞, 李志加, 苏镇军, 段晓辉, 韩维文, 王云晓, 贺晓磊, 吕林林, 贾金海. 血清谷胱甘肽过氧化物酶与晚期非小细胞肺癌患者临床病理指标及预后的相关性[J]. 癌变·畸变·突变, 2021, 33(4): 286-290,295.
[4]	徐启璐, 高慧, 冉学红, 王军军, 张俊英, 刘丽萍. 两种异常核型髓系肿瘤的基因突变及临床相关性分析[J]. 癌变·畸变·突变, 2021, 33(4): 296-301,306.
[5]	王熙凯, 孟庆贺, 高燕鲁. miR-223-3p通过调控ECT2诱导非小细胞肺癌细胞凋亡的实验研究[J]. 癌变·畸变·突变, 2021, 33(3): 187-192.
[6]	张玉铃, 吴俊东, 潘东岳, 陈春发. 乳腺癌新辅助化疗前后Ki67变化对疗效及预后的意义[J]. 癌变·畸变·突变, 2021, 33(3): 230-235,245.
[7]	焦文静, 郭秀娟, 马鸣, 邵俊国, 张金艳. 老年局部晚期食管癌同步放化疗与单纯放疗的疗效比较[J]. 癌变·畸变·突变, 2021, 33(2): 124-128.
[8]	赵子慧, 王绪华. 非小细胞肺癌伴随诊断的研究进展[J]. 癌变·畸变·突变, 2021, 33(1): 66-71,76.
[9]	黎梓蕊, 许键, 李红文, 张鹏. 口腔癌相关microRNA的研究进展[J]. 癌变·畸变·突变, 2020, 32(6): 481-484.
[10]	刘晓霞, 李卫霞, 苏镇军, 贾金海, 段晓辉, 李志加, 贺晓磊, 吕林林, 刘睿, 王云晓. 晚期非小细胞肺癌病理特征及放化疗联合治疗疗效与患者血清超氧化物歧化酶的关系[J]. 癌变·畸变·突变, 2020, 32(5): 350-354.
[11]	张佳虹, 张庆英, 张燕虹, 陈甲连, 谢芳, 刘锐国, 吴容, 吴龙飞. 一个家族性高胆固醇血症家系的基因突变筛查与评估[J]. 癌变·畸变·突变, 2020, 32(3): 229-232,245.
[12]	曹易懿, 刘维映, 尤馨悦, 奚晶, 陈瑞雪, 张新宇, 栾洋. 多溴联苯醚BDE-3、BDE-47和BDE-209的体外遗传毒性评价[J]. 癌变·畸变·突变, 2020, 32(1): 15-20,28.
[13]	陈秀琼, 孟凡桥, 熊华, 周洋媚, 唐雯华, 邹燕梅. 转移性结直肠癌抗EGFR治疗的耐药机制研究进展[J]. 癌变·畸变·突变, 2020, 32(1): 67-71.
[14]	陈高峰, 王亚楠, 王丹, 毛志慧, 黄芝瑛, 文海若, 王雪. Pig-a基因突变试验研究进展[J]. 癌变·畸变·突变, 2019, 31(6): 492-497.
[15]	马阳, 吴娟, 纪晓坤, 王蕊, 杜芸, 王珩, 郭晓, 张艳. 沉默表皮生长因子受体的表达对肺腺癌A549细胞自噬的影响[J]. 癌变·畸变·突变, 2019, 31(5): 347-351,358.