背景与目的 随着基因突变技术及靶向药物治疗如火如荼的开展,对肺腺癌的精准治疗越来越受到关注,目前肺腺癌中研究最多的是表皮生长因子受体(epidermal growth factor receptor,EGFR).对于EGFR突变和病理分型的关系在不同标本中是否一致,目前不甚明了.本研究比较肺腺癌活检标本和手术切除标本中EGFR基因突变与病理分型的关系是否一致,探讨EGFR基因突变与肺腺癌病理分型的关系以及标本类型对EGFR基因检测的影响.方法 收集肺腺癌手术切除标本(楔形肺切除、肺叶切除标本)163例,肺腺癌活检[粘膜活检、肺穿刺、支气管内超声引导针吸活检术(endobronchial ultrasound-guided transbronchial needle aspiration,EBUS-TBNA)标本]173例,按照2015年世界卫生组织(World Health Organization,WHO)肺腺癌分型标准对其主要组织学分型确认(贴壁型、腺泡型、乳头型、微乳头型、实体型),行EGFR基因检测[基因测序法及突变扩增阻滞系统(amplification refractory mutation system,ARMS)].分别对活检标本和手术切除标本进行统计.结果163例的肺腺癌手术切除标本中,102例EGFR基因突变,突变率为62.58%,173例的活检标本中,114例EGFR基因突变,突变率为65.9%.两组标本中EGFR突变率没有统计学差异(P>0.05).两组标本中女性的EGFR突变率均明显高于男性(P<0.05).手术切除标本中60岁以上患者的EGFR突变率明显低于60岁以下(P<0.05),而活检标本中EGFR突变与年龄无关(P>0.05).在EGFR突变的两组标本中病理分型构成比不同(χ2=8.040,P<0.05).手术切除标本肺腺癌中EGFR突变的102例中,腺泡型占54.9%(56例),贴壁型占23.53%(24例),乳头型占17.65%(18例),实体型占3.9%(4例),其中腺泡型所占比例最高,其次是贴壁型和乳头型,实体型则比例最少.19、21外显子单独突变最多,21外显子突变在贴壁型较其他两型高(P<0.05),19外显子突变在乳头型较贴壁型高(P<0.05).腺泡型和乳头型比较,19、21外显子突变无统计学意义.活检标本肺腺癌中EGFR突变的114例中腺泡型占48.25%(55例),贴壁型占26.32%(30例),乳头型占11.4%(13例),微乳头型占4.39%(5例),实体型占9.65%(11例).腺泡型所占比例最高,其次是贴壁型,乳头状、微乳头状和实体型最少.同样是19、21外显子单独突变最多,但不同病理分型中,19、21外显子突变均无显著差异(P>0.05).结论 肺腺癌中手术切除标本和活检标本EGFR突变率没有差异,且突变与性别有关,均为女性突变率高于男性.手术切除标本中EGFR突变与年龄有关,年龄越大突变率越低,而在活检标本中则与年龄无关.两组标本的病理分型构成比不同.19、21外显子单独突变最多.手术切除标本中EGFR突变类型与主要病理分型有关,21外显子单独突变中贴壁型最多,19外显子单独突变中乳头型最多.EGFR突变活检标本中,19、21外显子单独突变与主要病理分型无明显相关.%Background and objective With the development of genetic mutations and targeted drugs, ac-curate therapy of lung adenocarcinoma attracts much more attention, and more research is focued on epidermal growth factor receptor (EGFR). It is unclear whether the result of EGFR mutation and pathology type is consistent with differ-ent specimens. In our study, by comparing the relationship between EGFR mutations and pathological classification of lung adenocarcinoma in surgical resection of specimen and biopsy specimen, to discuss the relationship between EGFR mutations and pathological classification of and the influence of specimen type on EGFR gene detection. Methods A total of 163 cases of surgical resection of sample of lung adenocarcinoma (pulmonary resection and pulmonary lobec-tomy) and 173 cases of biopsy specimen [mucosa biopsy, needle biopsy of lung, and endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA)] were performed by gene sequencing method and amplification refractory mutation system (ARMS) and the majority of the type was confirmed (lepidic, acinar, papillary, micropapil-lary, solid) according to the classification of lung adenocarcinoma in 2015 World Health Organization (WHO). The statistics was used in surgical and biopsy sample respectively. Results The gene mutation of EGFR in surgical and bi-opsy sample of lung adenocarcinoma was 62.58% (102/163) and 65.9% (114/173) respectively, and no significant dif-ference was found (P>0.05). The mutation of EGFR in female was predominant both of the two groups (P<0.05). The mutation rate of EGFR over the age of 60 was significantly lower than that below 60 in surgical specimen, while it was not related to age in biopsy sample. The constituent ratio of pathology type was different in the two groups (χ2=8.04, P<0.05). Among 102 cases of lung adenocarcinoma in surgical specimen, the acinar took up the highest proportion (54.9%), followed by the lepidic (23.53%) and the papillary (17.65%). The solid adenocarcinoma accounted for the minimal percentage (3.9%). The mutation of 19 and 21 exon alone was most common. The mutation rate of 21 exon in the lepidic was higher than that in the acinar and papillary (P<0.05), but the mutation rate of 19 exon in the papil-lary was higher than that in the lepidic (P<0.05). There was no significant difference of 19 and 21 exon in the acinar and papillary. Among 114 cases of lung adenocarcinoma in the biopsy specimen, the most percentage was the acinar (48.25%), the lepidic was secondly, and the papillary, micropapillary and solid adenocarcinoma was the minimal. The exon mutation of 19 and 21 exon alone was most common, while no obvious difference of 19 and 21 exon was found in different pathology classifications (P>0.05). Conclusion The mutation rate of EGFR of lung adenocarcinoma in surgical resected specimen and biopsy specimen was not found difference, which was related to sex, and the female was predominant. The mutation rate of surgical specimen was higher in the young, while that of biopsy specimen was not related to the age. Apparent difference of the pathology type proportion was found in the two groups. The mutation of 19 and 21 exon alone was most common. The mutation of EGFR in surgical specimens was related to pathology types. The percentage of the lepidic adenocarcinoma was highest in the mutation of 21 exon alone. Among the mutation of 19 exon alone, the papillary was predominant. There was no obvious relationship between the mutation of 19 and 21 exon alone and pathology type in biopsy sample.
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