EGFR基因突变与肺腺癌主要病理分型及标本类型的关系

发布时间：2018-06-11 20:47

本文选题：肺腺癌 + EGFR　；参考：《中国肺癌杂志》2017年06期

【摘要】：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,EBUSTBNA)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(P0.05)。两组标本中女性的EGFR突变率均明显高于男性(P0.05)。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(P0.05),而活检标本中EGFR突变与年龄无关(P0.05)。在EGFR突变的两组标本中病理分型构成比不同(χ2=8.040,P0.05)。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(P0.05),19外显子突变在乳头型较贴壁型高(P0.05)。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(P0.05)。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。
[Abstract]:Background & objective with the development of gene mutation and targeted drug therapy, more and more attention has been paid to the accurate treatment of lung adenocarcinoma. At present, epidermal growth factor receptor (EGFR) is the most widely studied in lung adenocarcinoma. It is not clear whether the relationship between EGFR mutation and pathological typing is consistent in different specimens. The aim of this study was to compare the relationship between EGFR gene mutation and pathological typing in lung adenocarcinoma biopsy specimens and surgical resection specimens, and to explore the relationship between EGFR gene mutation and pathological classification of lung adenocarcinoma and the effect of specimen type on the detection of EGFR gene. Methods 173 cases of lung adenocarcinoma underwent surgical resection (wedge pneumonectomy and lobectomy) and biopsy of lung adenocarcinoma (mucosal biopsy, lung puncture, intrabronchial ultrasound guided needle aspiration) were collected. According to the 2015 World Health Organization (WHO) criteria for the classification of lung adenocarcinoma, the main histological types were confirmed (adherent type, acinar type, papillary type, micronipple type). EGFR gene was detected by gene sequencing and mutation amplification block system amplification (refractory mutation system ARMS). Biopsy specimens and surgical excision specimens were statistically analyzed. Results there were 102 cases of EGFR gene mutation in 163 surgical specimens of lung adenocarcinoma. The mutation rate of EGFR gene was 62.58 and 114 out of 173 biopsy samples, the mutation rate was 65.9%. There was no significant difference in EGFR mutation rate between the two groups (P 0.05). The EGFR mutation rate in both groups was significantly higher than that in males. The mutation rate of EGFR in patients over 60 years of age was significantly lower than that in patients under 60 years old, while in biopsy specimens there was no correlation between EGFR mutation and age. In the two groups of EGFR mutation, the ratio of pathological typing was different (蠂 ~ 2 = 8.040) (P = 0.05). Among 102 cases of lung adenocarcinoma with EGFR mutation, 56 cases were acinar type, 24 cases were adherent type, 18 cases were papillary type, 4 cases were solid type, among which acinar type was the most common type, followed by adherent type and papillary type. In solid type, the proportion of single mutation in exon .19 was the least. The mutation of exon 1 was the highest in the adherent type than in the other two types. The mutation of exon 19 in the papillary type was higher than that in the adherent type. There was no significant difference between acinar type and papillary type. Among 114 cases of EGFR mutation in biopsy specimens, 55 cases were acinar type, 30 cases were adherent type, 13 cases were papillary type, 5 cases were micropapillary type, and 11 cases were solid type. The proportion of acinar type was the highest, followed by adherent type, papillary type, micropapillary type and solid type. The single mutation of exon 19M21 was also the most, but there was no significant difference in the mutation of exon 1921 in different pathological types (P0. 05). Conclusion there is no difference in EGFR mutation rate between surgical and biopsy specimens in lung adenocarcinoma, and the mutation rate is related to sex, and the mutation rate of female is higher than that of male. EGFR mutation was associated with age in surgical excision specimens, the higher the age, the lower the mutation rate, but not the age in biopsy specimens. The ratio of pathological types of the two groups was different. The single mutation of exon 19 ~ (21) was the most. The types of EGFR mutations in surgical exons are related to the main histopathological types. In the single mutation of exon 21, the most adherent type of exon 19 is the largest in the single mutation of papillary type. EGFR mutation in biopsy specimens with single mutation of exon 19 and the main pathological changes of exon 19 is related to the type of EGFR mutation. There was no significant correlation in typing.
【作者单位】：北京大学医学部病理学系;河北省胸科医院病理科;
【基金】：国家自然科学基金项目(No.81300045)资助~~
【分类号】：R734.2

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