EGFR基因突变与EGFR酪氨酸激酶抑制剂近期疗效的关系

背景与目的 多项研究证实表皮生长因子受体(epidermal growth factor receptor,EGFR)突变与EGFR酪氨酸激酶抑制剂(tyrosine kinase inhibitor,TKI)的疗效存在相关性.本研究应用荧光定量PCR技术检测晚期肺癌的EGFR基因突变,分析其与EGFR TKI药物Gefitinib二线治疗晚期非小细胞肺癌(nonsmall cell lung cancer,NSCLC)的近期疗效之间的关系.方法 从63例血浆和胸腔积液标本(其中血浆53例,胸腔积液10例)中提取游离DNA,应用荧光定量PCR技术进行EGFR 18、19、21外显子基因的检测,并结合临床进行分析.结果 在63例血浆和胸腔积液标本中检测到EGFR基因突变17例,突变率为27.0%.EGFR基因突变主要见于女性及非吸烟人群(P＜0.05).存在EGFR基因突变的患者Gefitinib二线治疗的疗效明显优于野生型患者(P＜0.01).结论 晚期NSCLC患者的血浆、胸腔积液游离DNA中存在EGFR基因突变,这类突变可以通过荧光定量PCR技术检测出来.EGFR基因突变患者对Gefitinib的反应率明显高于野生型患者,检测胸腔积液和/或血浆EGFR基因突变有助于选择有效患者接受EGFR TKI治疗.     

湖北十堰地区非小细胞肺癌患者表皮生长因子受体基因突变情况分析

目的探讨湖北十堰地区非小细胞肺癌(NSCLC)患者表皮生长因子受体(EGFR)基因突变情况及其与患者临床病理特征的关系。方法回顾性分析2017年11月至2020年1月就诊于湖北医药学院附属国药东风总医院的173例NSCLC患者资料。通过突变扩增阻滞系统(ARMS)-TaqMan探针法检测NSCLC组织中EGFR基因突变情况, 同时收集患者的临床病理资料, 分析EGFR基因突变状态与患者临床病理特征之间的关系。结果 173例样本中76例发生EGFR基因突变, 突变率为44.5%。其中第18号外显子突变率为6.6%(5/76), 均为G719X突变;第19号外显子突变率为46.1%(35/76), 均为Del突变;第20号外显子突变率为1.3%(1/76), 为EGFR基因20ins突变;第21号外显子突变率为44.7%(34/76), 其中33例为EGFR基因L858R突变, 1例为EGFR基因L861Q突变;1例为第19号外显子Del合并第20号外显子T790M双重突变。不同性别、吸烟史、病理分型的患者EGFR突变率比较差异均有统计学意义(均P<0.05), 女性患者高于男性患者...     

EGFR突变与肺癌伴恶性胸腔积液患者生物学行为的相关性研究

目的 探讨表皮生长因子受体(EGFR)基因突变与肺癌伴恶性胸腔积液患者生物学行为之间的关系.方法 选取肺癌患者100例,其中伴恶性胸腔积液者43例作为观察组,不伴胸腔积液者57例作为对照组,观察两组患者EGFR基因突变情况.结果 观察组EGFR总突变率为72.09%,高于对照组的19.30%(P﹤0.05);观察组高分化、中分化和低分化患者的EGFR突变率分别为69.23%、71.43%和77.78%,均高于对照组高分化、中分化和低分化患者(P﹤0.05);不同性别、年龄、吸烟情况及分化程度的观察组患者EGFR基因突变率比较,差异均无统计学意义(P﹥0.05);胸腔积液与活检组织标本EGFR基因检测结果的Kappa值为0.466(P﹤0.05),一致性中等.结论 肺癌伴恶性胸腔积液患者EGFR突变率较高,但EGFR突变与肺癌伴恶性胸腔积液患者的性别、年龄、吸烟情况及分化程度无关.     

超声引导下肺肿块粗针活检在NSCLC患者EGFR 基因突变检测中的价值

目的探究超声引导下肺肿块粗针活检在非小细胞肺癌(NSCLC)患者表皮生长因子受体(EGFR)基因突变检测中的价值。方法回顾性分析96例NSCLC患者临床资料。96例NSCLC患者均采用超声引导下肺肿块粗针活检,分析穿刺成功率及EGFR基因突变检测结果。结果 96例患者均采用16G粗针活检,并顺利完成穿刺活检,取材满意率100.00%;96例患者病理均确诊为NSCLC,其中腺癌、鳞癌、腺鳞癌、肉瘤样癌各有77例、6例、8例、5例。穿刺术后有1例患者出现咯血,采用止血药物治疗后缓解;2例患者出现针道少许渗血,但未做特殊处理,观察1～2 h后无不适反应。96例NSCLC患者中检测EGFR基因突变有44例,突变率为45.83%(44/96),其中20例为外显子19突变;16例为外显子21突变,4例为外显子20突变,4例为外显子20、21均突变。结论超声引导下肺肿块粗针活检有利于准确诊断NSCLC并检测EGFR基因突变情况,是一种安全有效的取材手段,具有临床应用安全、简便且易于推广等优势,可为临床分子靶向药物的治疗提供确切依据。     

TaqMan-MGB探针实时荧光聚合酶链反应快速检测非小细胞肺癌表皮生长因子受体基因突变

目的探讨非小细胞肺癌(NSCLC)瘤组织表皮生长因子受体(EGFR)基因突变及TaqMan MGB探针实时荧光PCR快速检测EGFR突变的诊断价值。方法应用聚合酶链(PCR)反应,对80例手术切除NSCLC瘤组织EGFR基因的第18、19和21外显子片段进行扩增和测序, Chromas软件分析基因突变。设计EGFR突变位点的TaqMan MGB探针,采用实时PCR检测瘤组织EGFR突变,并与测序结果比较。实时PCR的敏感性与特异性评价,用不同混合数量的PC-9细胞(19外显子缺失)为阳性参照。结果21例NSCLC瘤组织存在EGFR基因突变,总体突变率为26.3%。其中13例为EGFR第19外显子阅读框内多核苷酸的缺失,8例为第21外显子2573位核苷酸点突变。诊断的特异性与敏感性均为100%。当PC-9突变型细胞仅占10%时或PC-9细胞数低达50只时,PCR仍然检测到EGFR基因突变的存在。女性、不吸烟和肺腺癌患者EGFR基因突变率显著高于男性、吸烟和非腺癌患者(P<0.05)。EGFR基因突变与患者年龄、TNM分期等因素无关。结论NSCLC存在EGFR基因的突变或缺失,其中以女性、腺癌和不吸烟患者突变率较高。TaqMan MGB探针联合实时PCR可有效地检测出EGFR基因突变,操作简便,易于临床推广。     

扩增阻滞突变系统法检测非小细胞肺癌微小标本表皮生长因子受体突变

目的:探讨非小细胞肺癌(non-small cell lung cancer,NSCLC)微小标本代替大体标本用于扩增阻滞突变系统(ampli cation refractory mutation system,ARMS)法检测表皮生长因子受体(epidermal growth factorreceptor,EGFR)基因突变的可行性。方法:181例NSCLC标本纳入本研究,包括157例微小标本(分别为CT引导下经皮肺穿刺活检标本、支气管内超声引导下针吸活检标本、淋巴结活检标本、支气管镜活检标本和胸腔积液)和24例大体标本。采用QIAGEN DNA提取试剂盒提取标本组织DNA,然后使用AmoyDx人类EGFR基因4种突变荧光PCR检测试剂盒检测EGFR基因的突变情况,最后采用χ2检验或Fisher精确检验比较微小标本与大体标本的EGFR突变检出率。结果:181例标本中,EGFR的总突变率为39.8%(72/181);其中微小标本的EGFR突变检出率为38.9%,大体标本的EGFR突变检出率为45.8%,2者间差异无统计学意义(P=0.515)。EGFR突变率在不吸烟患者(P=0.033)和腺癌患者(P<0.001)中显著增高。结论:ARMS法检测NSCLC微小标本也能获得较高的EGFR突变检出率。对于晚期难以获得大体标本的NSCLC患者,微小标本可代替大体标本应用于临床EGFR突变检测。     

EGFR基因突变与肺腺癌主要病理分型及标本类型的关系

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.     

ADx-ARMS方法检测晚期非小细胞肺癌患者胸水标本癌细胞基因突变的临床意义

目的:探讨应用ADx-ARMS方法检测非小细胞肺癌患者胸水标本癌细胞基因突变应用于指导小分子EGFR酪氨酸激酶抑制剂（EGFR-TKIs）治疗的可行性与临床意义。方法:ADx-ARMS检测24例非小细胞肺癌患者胸水标本EGFR基因第19、20和21外显子突变与KRAS基因第2外显子突变。统计分析胸水标本与前期检测过的非小细胞肺癌组织中的EGFR、KRAS突变率差异。结果:24例胸水标本中,EGFR突变与KRAS突变分别为14例（58.3%）和1例（4.2%）。前期检测过的非小细胞肺癌组织EGFR和KRAS突变率分别为47.6%和4.5%。EGFR和KRAS突变率在胸水标本与前期肺癌组织中差异无统计学意义（P>0.05）。结论:对失去手术机会而难以获得组织标本的晚期非小细胞肺癌患者,可应用ADx-ARMS方法选择胸水标本筛查EGFR、KRAS基因突变,从而指导EGFR-TKIs的临床应用。     

非小细胞肺癌EGFR基因突变的临床意义研究

  目的   探讨非小细胞肺癌EGFR基因外显子突变与其临床病理特征的关系。   方法   利用ADx-ARMS?EGFR基因突变检测试剂盒,检测214例未接受过Gefitinib治疗的非小细胞肺癌患者组织中EGFR基因外显子18、19、20和21突变。   结果   非小细胞肺癌组织中EGFR基因总突变率为45.8%（98/214）,外显子18、19、20和21的突变率分别为0.93%（2/214）、22.0%（47/214）、2.3%（5/ 214）和20.6%（44/214）。另有2例19和21外显子双重突变。EGFR基因在肺腺癌组织中的总突变率为50.3%（93/185）明显高于肺鳞状细胞癌17.2%（5/29）（P=0.001）。EGFR基因在女性患者中的突变率57.0%（57/100）高于男性36.0%（41/114）（P=0.002）,EGFR基因在NSCLC淋巴结转移患者中的突变率（66.7%）显著高于无淋巴结转移患者（39.5%）（P < 0.05）,但EGFR基因突变率与肺癌患者的年龄、肿瘤分级和临床分期均无显著性差异（P>0.05）。   结论   中国肺癌尤其是肺腺癌患者存在EGFR基因的较高突变率,EGFR外显子19、21突变结合肺癌的临床病理特征有望成为评估TKI治疗非小细胞肺癌疗效的分子标志。      

非小细胞肺癌胸腔积液与配对肿瘤组织中EGFR基因突变检测的比较

目的:探讨非小细胞肺癌胸腔积液与配对肿瘤组织标本中EGFR基因突变检测结果的一致性,评价胸腔积液标本检测EGFR基因突变的应用价值.方法:收集非小细胞肺癌患者胸腔积液与配对肿瘤组织样本72例,采用ARMS方法,检测样本中EGFR基因第18~21外显子突变情况.结果:细胞学样本和组织学样本中EGFR基因突变阳性率分别为48.61%和51.39%,两者差异无统计学意义(P>0.05),二者一致率为92.11%,不一致率为7.89%.结论:二者的一致率较高,恶性胸水可以作为无法获得肿瘤组织的晚期非小细胞肺癌EGFR基因检测的有效样本.     

High Feasibility of Liquid-Based Cytological Samples for Detection of EGFR Mutations in Chinese Patients with NSCLC

Background: Activating mutations of epidermal growth factor receptor (EGFR) could predict response totyrosine kinase inhibitor (TKI) treatment in patients with non-small cell lung cancer (NSCLC). However, thedetection of EGFR mutation is frequently challenging in clinical practice for the lack of tumor tissue. The aim ofthis study was to investigate the feasibility of performing EGFR mutation testing on various types of liquid-basedcytology (LBC) samples. Materials and Methods: A total of 434 liquid-based cytology samples were collectedfrom March 2010 and November 2013. Among them, 101 with diagnosis of lung adenocarcinoma had pairedsurgically resected specimens. The ADx Amplification Refractory Mutation System (ADx-ARMS) was used todetermine EGFR mutation status both in LBC and resected samples. Results: All liquid-based cytology sampleswere adequate for EGFR mutation analysis. The mutation rate was 50.5% in the 434 NSCLC patients with LBCsamples and the incidence rates of EGFR mutation were consistent among different specimens. We also detectedEGFR positives in 52.5% (53/101) patients with paired histologic specimens. The concordance rate of EGFRmutation between LBC samples and paired histologic specimens was 92.1%. Conclusions: Our results suggestthat liquid-based cytology samples are highly reliable for EGFR mutation testing in patients with NSCLC.     

Epidermal growth factor receptor mutations in needle biopsy/aspiration samples predict response to gefitinib therapy and survival of patients with advanced nonsmall cell lung cancer

Recently, mutations in the epidermal growth factor receptor (EGFR) gene in nonsmall cell lung cancer (NSCLC) patients were reported to correlate with gefitinib response. Less than 30% of NSCLC patients are surgically resectable; however, molecular analysis has to rely on nonsurgical diagnostic tissue samples. The objective of this study is to investigate EGFR mutation analysis on needle biopsy/aspiration samples and its correlations with gefitinib response and patients' survival. EGFR mutation was assessed from DNA of 63 paraffin-embedded small needle biopsy/aspiration specimens from 62 patients with NSCLC treated with gefitinib. The peripheral blood lymphocyte DNA of the patients was sequenced to verify the EGFR mutation. EGFR mutations were found in 47% of 62 patients (60% of 20 CT-guided biopsies, 44% of 18 ultrasound-guided biopsies, 31% of 16 endoscopic biopsies and 44% of 9 effusion cell blocks). EGFR mutations were frequently present in females (p = 0.006) and never smokers (p = 0.04). Patients with EGFR mutations had a significantly better response rate compared to that of the nonmutation group (p < 0.001). Multivariate analysis showed that EGFR mutation (p < 0.001) and PS 0-1 (p = 0.02) were independently associated with a better response rate. Cox regression analysis showed that EGFR mutation was the independent prognostic factor for progression-free survival (p = 0.008) and overall survival (p = 0.03). In conclusion, EGFR mutation analysis is feasible in needle biopsy/aspiration paraffin-fixed specimens. EGFR mutation is an independent predictor of gefitinib response and survival in patients of advanced NSCLC treated by gefitinib.     

High sensitivity detection of epidermal growth factor receptor mutations in the pleural effusion of non-small cell lung cancer patients

Epidermal growth factor receptor (EGFR) mutations are a strong determinant of tumor response to gefitinib in non-small cell lung cancer (NSCLC). We attempted to elucidate the feasibility of EGFR mutation detection in cells of pleural effusion fluid. We obtained 24 samples of pleural effusion fluid from NSCLC patients. The pleural effusion fluid was centrifuged, and the cellular components obtained were used for detection. EGFR mutation status was determined by a direct sequencing method (exons 18-21) and by the Scorpion Amplified Refractory Mutation System (ARMS) method. EGFR mutations were detected in eight cases. Three mutations were detected by both methods, and the other five mutations were detected by Scorpion ARMS alone. The mutations were detected by both methods in all four partial responders among the seven patients who received gefitinib therapy. Direct sequencing detected the mutations in only two of four cases with partial response. These results suggest that the DNA in pleural effusion fluid can be used to detect EGFR mutations. The Scorpion ARMS method appears to be more sensitive for detecting EGFR mutations than the direct sequencing method.     

EGFR mutation status in tumour-derived DNA from pleural effusion fluid is a practical basis for predicting the response to gefitinib

Epidermal growth factor receptor (EGFR) mutations are strong determinants of tumour response to EGFR tyrosine kinase inhibitors in non-small-cell lung cancer (NSCLC). Pleural effusion is a common complication of lung cancer. In this study, we assessed the feasibility of detection of EGFR mutations in samples of pleural effusion fluid. We obtained 43 samples, which was the cell-free supernatant of pleural fluid, from Japanese NSCLC patients, and examined them for EGFR mutations. The epidermal growth factor receptor mutation status was determined by a direct sequencing method (exons 18-21 in EGFR). EGFR mutations were detected in 11 cases (E746_A750del in seven cases, E746_T751del insA in one case, L747_T751del in one case, and L858R in two cases). The EGFR mutations were observed more frequently in women and non-smokers. A comparison between the EGFR mutant status and the response to gefitinib in the 27 patients who received gefitinib revealed that all seven patients with partial response and one of the seven patients with stable disease had an EGFR mutation. No EGFR mutations were detected in the patients with progressive disease. The results suggest that DNA in pleural effusion fluid can be used to detect EGFR mutations and that the EGFR mutation status may be useful as a predictor of the response to gefitinib.     

Detection of EGFR gene mutation in lung cancer by mutant-enriched polymerase chain reaction assay.

PURPOSE: Mutations in the epidermal growth factor receptor (EGFR) gene have been reported to be present in non-small cell lung cancer (NSCLC) and related to the responsiveness of tumors to EGFR tyrosine kinase inhibitors, suggesting its usefulness as a biomarker. Because clinical samples contain tumor and normal cells or genes, a highly sensitive assay for detecting mutation is critical for clinical applications. EXPERIMENTAL DESIGN: The mutant-enriched PCR is a rapid and sensitive assay with selective restriction enzyme digestion. We developed the mutant-enriched PCR assay targeting exons 19 and 21 of EGFR and applied the developed assay to detect mutations in 108 cases of surgically resected specimens of NSCLCs, 18 samples of computed tomography (CT)-guided needle lung biopsies, and 20 samples of pleural fluid. In addition, results were then compared with those from direct sequencing and a nonenriched PCR assay. RESULTS: The mutant-enriched PCR that was proved to enrich one mutant of 2 x 10(3) normal genes detected mutations in 37 cases of 108 resected tumors, seven samples of CT-guided lung biopsies, and seven samples of pleural fluid. Among mutant cases, four resected tumors, two CT-guided lung biopsies, and two pleural fluid were identified as additional mutant cases by the mutant-enriched PCR, which were considered normal based on nonenriched assays. CONCLUSIONS: Our results indicate that EGFR mutations are readily detectable by mutant-enriched PCR in various clinical samples. Thus, mutant-enriched PCR may provide a valuable method of potentially detecting a small fraction of mutant genes in heterogeneous specimens, indicating its possible use in clinical application for NSCLC.     

Analysis of EGFR Mutation Status in Algerian Patients with Non-Small Cell Lung Cancer

Background and objective: Epidermal growth factor receptor (EGFR) mutation status is used as a predictive biomarker for the tyrosine kinase inhibitors therapy in non-small cell lung cancer (NSCLC). The incidence of EGFR mutations appears to vary according to ethnic and geographical backgrounds. This retrospective study aimed to investigate the EGFR mutation status in Algerian NSCLC patients and its association with clinicopathological features. Methods: We examined the presence of EGFR mutations (Exons 19-21) in 58 unselected  NSCLC samples using PCR followed by direct sequencing. Results: The present study included 53 (91.4%) men and 5 (8.6%) women, with a median age of 59 (ranging from 44 to 94 years old). EGFR mutations were detected in 23 patients, with an overall rate of 39.6%. There were 21 (91.3%) cases with the exon-21 L585R single mutation and two (8.7%) with dual mutations of exon-19 deletions and L585R. EGFR mutations were more frequently found in patients with confirmed adenocarcinoma (14/27, 51.8%) than in non-adenomatous NCSCL subtypes (3/14, 21.4%; p=0.03). Furthermore, early stages of the disease were significantly associated with a higher rate of EGFR mutations (14/27, 51.8%) compared with those at  advanced stage (5/21, 23.8%; p=0.02). There were no significant differences in EGFR mutation frequency by age, gender, or smoking status. Conclusion: We found that Algerian NSCLC patients exhibited a high rate of EGFR mutations, which was quite similar to that in Asians population rather than Caucasian patients. Thus, TKI-based treatments may be more beneficial for Algerian patients with NSCLC. Further studies using a large number of patients are required to confirm our preliminary findings.     

EGFR mutations predict a favorable outcome for malignant pleural effusion of lung adenocarcinoma with Tarceva therapy

The aim of the present study was to evaluate the therapeutic effects and adverse reactions of Tarceva treatment for malignant pleural effusion (MPE) caused by metastatic lung adenocarcinomas. One hundred and twenty-eight patients who failed first-line chemotherapy drug treatment were divided into a mutation and a non-mutation group according to the presence or absence of epidermal growth factor receptor (EGFR) mutations. Each patient received closed drainage combined with simple negative pressure suction after thoracoscopic talc poudrage pleurodesis and oral Tarceva treatment. Short-term and long-term clinical therapeutic effects of Tarceva were evaluated. The EGFR mutation rate in pleural metastatic tissues of lung adenocarcinoma acquired through video-assisted thoracoscopic surgery was higher compared to that in surgical resection specimens, plasma specimens and pleural effusion specimens compared to previously reported results. There were significant statistical differences in the average extubation time (p<0.01), drainage volume of pleural effusion (p<0.05), Karnofsky score and formation of encapsulated pleural effusion 4 weeks after surgery (p<0.05) between these two groups. The number of patients with mild pleural hypertrophy in the mutation group was significantly higher compared to the non-mutation group (p<0.01), while the number of patients with severe pleural hypertrophy was significantly reduced (p<0.05). There was significant statistical discrepancy between these two groups in terms of improvement of peripheral blood carcinoembryonic antigen and tissue polypeptide antigen after 4 weeks of therapy. The complete remission rate and the efficacy rate were higher in the mutation group compared to that in the non-mutation group (p<0.05). There was a longer overall survival time after Tarceva treatment in patients with EGFR mutations than those without EGFR mutation. EGFR mutations predict a favorable outcome for malignant pleural effusion of lung adenocarcinoma with Tarceva therapy. Detection of EGFR mutations may determine the responsiveness of malignant pleural effusion to Tarceva treatment.     

非小细胞肺癌E GF R基因突变的表现及其与肿瘤标记物的相关性

目的：探讨非小细胞肺癌（NSCLC）EGFR基因突变位点状态,分析其与血清肿瘤标记物NSE、CEA、CYFRA21－1、TSGF间的关系。方法：回顾性分析240例NSCLC患者组织标本中EGFR不同位点基因突变状态,分析基因突变率与患者性别、年龄、吸烟史和组织分型间的关系及NSCLC患者19、21突变位点与肿瘤标记物NSE、CEA、CYFRA21－1、TSGF的相关性。结果：240例标本突变135例,18号外显子突变2例（1．5％）;19号外显子突变47例（34．8％）;20号外显子突变7例（5．2％）;21号外显子突变71例（52．6％）;双突变8例（5．9％）。EGFR突变主要发生在19、21号外显子上,其中19号外显子突变与组织分型有关（P＜0．05）,与年龄、性别、吸烟史无关（P＞0．05）;21号外显子突变与组织分型、吸烟史、性别有关（P＜0．05）,与年龄无关（P＞0．05）。EGFR突变组肿瘤标志物NSE、CEA、CYFRA21－1、TSGF的表达水平与未突变组之间差异无统计学意义（P＞0．05）,19、21号外显子突变的肿瘤标记物NSE、CEA、CYFRA21－1、TSGF之间的差异也无统计学意义（P＞0．05）。结论：NSCLC的EGFR突变中19、21号外显子突变率显著高于其他类型,这对于指导临床合理应用EGFR－TKIs药物治疗有重要的意义。而肿瘤标记物NSE、CEA、CYFRA21－1、TSGF在突变组与未突变组之间、19和21号外显子突变之间的差异均无统计学意义。因此,血清肿瘤标记物可能不足以作为评估EGFR突变的指标。