| Title | 表皮生长因子受体基因突变性抗体在肺腺癌中的表达 |
| Other Titles | Expression of epidermal growth factor receptor mutation specific antibodies in lung adenocarcinoma:evaluation of sensitivity, specificity and relationship to histologic subtypes |
| Authors | 赖玉梅 冯勤 孙宇 王萍 时云飞 赵敏 吴琪 李向红 |
| Affiliation | 100142开云app体育 肿瘤医院暨北京市肿瘤防治研究所病理科,恶性肿瘤发病机制及转化研究教育部重点实验室 |
| Keywords | 肺肿瘤 腺癌 受体,表皮生长因子 DNA突变分析 免疫组织化学 Lung neoplasms Adenocarcinoma Receptor,epidermal growth factor DNA mutational analysis Immunohistochemistry |
| Issue Date | 2016 |
| Publisher | 中华病理学杂志 |
| Citation | 中华病理学杂志.2016,45(9),606-611. |
| Abstract | 目的：评估表皮生长因子受体（ EGFR）基因突变性抗体在浸润性肺腺癌中表达的敏感性、特异性及其与组织类型的关系。方法应用EGFR第19号外显子（ E746-A750）和第21号外显子（ L858R）突变性抗体，在组织芯片中采用免疫组织化学检测884例肺腺癌的表达情况，探讨免疫组织化学表达与组织类型的关系，并通过与扩增阻滞突变系统（ARMS）-PCR法基因检测结果（177例）相比较，分析EGFR突变性抗体免疫组织化学表达的敏感性和特异性。结果884例浸润性肺腺癌病例中，EGFR第19号外显子E746-A750缺失检测显示，3＋病例7例（0.79％），2＋病例38例（4.30％），1＋和0病例分别为129例（14.59％）和710例（80.32％）；第21号外显子L858R点突变检测显示，3＋病例82例（9.28％），2＋病例93例（10.52％），1＋和0病例分别为82例（9.28％）和627例（70.93％）。两种抗体的阳性表达（≥1＋为阳性）均多见于附壁为主型、腺泡为主型和乳头为主型，而少见于实性为主型和浸润性黏液腺癌，二者在不同组织类型中的表达差异有统计学意义（P值分别为0.014和0.016）。与177例分子病理结果对比，当定义1＋至3＋均为阳性时，第19和21号外显子的特异性分别可达98.59％、92.98％，但敏感性相对较低，为62.86％和88.89％。当定义2＋、3＋为阳性时，两种抗体的特异性分别为99.30％和97.37％，而敏感性分别为25.71％和74.60％。当定义3＋为阳性而0～2＋均为阴性时，两种抗体的特异性均达100.0％，但敏感性很低（8.57％、34.92％）。第19号外显子E746-A750缺失的18例病例中，免疫组织化学（≥1＋为阳性）敏感性高达88.89％，而非15 bp的缺失或非E746-A750缺失的8例中除2例1＋外全部为0。结论 EGFR突变性抗体的表达多见于附壁为主型、腺泡为主型和乳头为主型而少见于实性为主型和浸润性黏液腺癌。与基因检测结果相比，EGFR突变性抗体具有较高的特异性，但敏感性偏低。对于免疫组织化学为3＋的病例，可直接判读为突变阳性，对于2＋病例判读为阳性的准确率近90％，但如条件允许仍建议行基因检测，对于1＋及阴性的病例，需进一步行基因检测。 To evaluate the expression of epidermal growth factor receptor (EGFR) mutation specific antibodies in invasive lung adenocarcinomas, and their sensitivity, specificity, as well as relationship to histological subtypes.Immunostaining with EGFR mutation-specific antibodies, del E746-A750 in exon 19 and L858R in exon 21, was performed in tissue microarrays of 884 cases of resection specimens to study the relationship between the immunophenotypes and morphologic subtypes. The sensitivity and specificity of the stains were compared with gene mutations detected by amplified refractory mutation system-polymerase chain reaction (ARMS-PCR).Of the 884 cases, the expression of del E746-A750 in exon 19 was 3+ , 2+ , 1+ and 0 in 7 cases (0.79%), 38 cases (4.30%), 129 cases (14.59%) and 710 cases (80.32%), respectively. For L858R in exon 21, 3+ , 2+ , 1+ and 0 staining were seen in 82 cases (9.28%), 93 cases (10.52%), 82 cases (9.28%) and 627 cases (70.93%), respectively. For both antibodies, positive expression (1+ or more) was mainly observed in lepidic, acinar and papillary predominant subtypes, and rarely seen in solid subtype or invasive mucinous adenocarcinoma (P=0.014 and 0.016). If 1+ to 3+ expression was set as positive, the specificity of exon 19/exon 21 reached 98.59%/92.98%, while the sensitivity was relatively lower (62.86%/88.89%). If 2+ to 3+ expression was read as positive, the specificity and sensitivity were 99.30%/97.37% and 25.71%/74.60% for exon 19/exon 21. If only 3+ expression was considered positive, the specificity was 100.0% for both antibodies, with a low sensitivity (8.57% for exon 19 and 34.92% for exon 21). Of the 18 cases with E746-A750 del in exon 19 based on molecular detection, the sensitivity of immunohistochemistry for exon 19 was 88.89% if a positive cutoff value ≥1+ was used; in contrast, of the 8 cases harboring other deletions in exon 19, only two cases were positive as 1+ .Both the EGFR mutation specific antibodies del E746-A750 in exon 19 and L858R in exon 21 demonstrate high specificity and relatively low sensitivity, and are mostly expressed in lepidic, acinar and papillary predominant subtypes, but rarely in solid subtype or invasive mucinous adenocarcinoma. For cases with 3+ expression, a mutational statue for EGFR is likely. For the 2+ positive cases, the accuracy to predict mutation almost reaches 90%, but molecular detection for confirmation is desirable. For the 1+ and negative cases, DNA-based test is essential to avoid false negativity. |
| URI | http://hdl.handle.net/20.500.11897/492712 |
| ISSN | 0529-5807 |
| DOI | 10.3760/cma.j.issn.0529-5807.2016.09.004 |
| Indexed | PubMed 中文核心期刊要目总览(PKU) 中国科技核心期刊(ISTIC) 中国科学引文数据库(CSCD) |
| Appears in Collections: | 北京肿瘤医院 |
