蝎形探针扩增阻滞突变系统检测肺癌患者血清与肿瘤组织中表皮生长因子受体基因突变

目的 应用蝎形探针扩增阻滞突变系统(Scorpions ARMS)检测肺癌患者血清游离DNA和肿瘤组织中表皮生长因子受体(EGFR)基因突变,探索二者间的一致性.方法 用硅胶膜离心柱法提取石蜡切片中DNA,比较硅胶膜离心柱法、酚氯仿法及磁珠法提取血清游离DNA的结果.应用Scorpions ARMS检测石蜡包埋肿瘤组织...     

非小细胞肺癌表皮生长因子受体双向基因测序研究

目的 探讨中国人非小细胞肺癌表皮生长因子受体（EGFR）第18、19、21外显子基因突变状态。方法 32例病理证实的非小细胞肺癌组织标本,通过模板DNA提取、定量和Touchdown PCR扩增EGFR exon18、19、21序列,进行正、负链基因测序分析,并与10例非小细胞肺癌患者血液标本对照。结果 32例非小细胞肺癌组织发现7例共9种突变,即已报道的5例19外显子缺失和未见报道的21exonT〉G（L833V）及A〉T（H835L）杂合性突变,另有2例内含子多态改变。中国人非小细胞肺癌突变率为28．1％（9／32）,肺腺癌突变率为31．6％（6／19）。结论 中国人非小细胞肺癌的EGFR突变率与已报道的亚洲人女性肺腺癌的突变率相似,但存在中国人自身新的突变位点（L833V和H835L）及内含子改变,该突变率与国内易瑞沙治疗非小细胞肺癌有效率基本吻合。     

非小细胞肺癌组织表皮生长因子受体基因突变的临床意义

目的探讨非小细胞肺癌(NSCLC)肿瘤组织表皮生长因子受体(EGFR)基因突变及其相关因素.方法抽取80例手术切除肿瘤组织DNA,采用巢式PCR方法对编码EGFR基因的第18、19和21外显子片段进行扩增和测序,用Chromas软件分析基因突变或缺失.结果21例肿瘤组织存在EGFR基因突变或缺失,发生率为26.25%,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2 573位核苷酸点突变.这些突变均为杂合子型.肺腺癌突变率为42.10%(16/38),显著高于鳞癌的9.68%(3/31)和鳞腺混合癌的18.2%(2/11)(χ2=9.702,P ＜0.01);女性患者突变率为48.28%(14/29),显著高于男性患者的13.73%(7/51)(χ2=11.4,P＜0.01);不吸烟者突变率为40%(16/40),显著高于吸烟者的12.50%(5/40)(χ2=7.812,P＜0.01).EGFR基因突变与患者年龄、TNM分期等因素无关.Logistic回归分析提示患者性别和组织类型是影响EGFR突变的2个主要因素.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.     

化疗对晚期非小细胞肺癌患者表皮生长因子受体基因突变状态的影响

目的 探讨化疗对晚期非小细胞肺癌(NSCLC)患者表皮生长因子受体(EGFR)基因突变状态的影响.方法 选取85例晚期NSCLC患者作为研究对象.化疗前、化疗4~6个周期后均采集所有研究对象的外周血,采用酶切富集联合变性高效液相色谱法(REDE-DHPLC)检测EGFR-19外显子、EGFR-21外显子的突变状态.结果 85例晚期NSCLC患者化疗前EGFR突变阳性率为55.29%(47/85),化疗4~6个周期后EGFR突变阳性率为35.29%(30/85),化疗前后EGFR突变阳性率比较差异有统计学意义(P<0.05).化疗前后共有37例晚期NSCLC患者发生EGFR突变,其中27例从EGFR突变阳性转为EGFR突变阴性,10例患者从EGFR突变阴性转为EGFR突变阳性,两种突变模式发生率比较差异有统计学意义(P<0.05).结论 晚期NSCLC患者化疗过程中EGFR突变状态可能会发生改变,因此在给予其靶向治疗前应重新对其进行EGFR突变检查.     

表皮生长因子受体在肺癌组织中的表达

目的 探讨肺癌组织中表皮生长因子受体（ＥＧＦＲ）的表达水平及其临床意义。方法 采用免疫组化ＡＢＣ法检测３９例肺良性疾病、９５例原发性肺癌及癌旁肺组织中ＥＧＦＲ的表达水平。结果 非小细胞肺癌（ＮＳＣＬＣ）组织ＥＧＦＲ表达阳性率为８７．９％（８０／９１），肺良性病变肺组织为１０．３％（４／３９），４例小细胞肺癌（ＳＣＬＣ）无ＥＧＦＲ表达。在ＮＳＣＬＣ中，距癌组织３ｃｍ以内癌旁肺组织ＥＧＦＲ阳性率为６３     

表皮生长因子受体在肺癌诊治中的研究

表皮生长因子受体（EGFR）近年来已成为肿瘤诊断及治疗的一个潜在靶点。本文对肺癌中EGFR的表达及其与肺癌患者的预后关系以及在肺癌诊治方面的研究进展作一概述。     

表皮生长因子受体在肺癌诊治中的研究

表皮生长因子受体(EGFR)近年来已成为肿瘤诊断及治疗的一个潜在靶点.本文对肺癌中EGFR的表达及其与肺癌患者的预后关系以及在肺癌诊治方面的研究进展作一概述.     

非小细胞肺癌表皮生长因子受体基因突变的临床意义

表皮生长因子受体（EGFR）酪氨酸激酶抑制剂（TKI）已成为晚期非小细胞肺癌标准二线或三线治疗;其疗效受EGFR基因突变等诸多因素的影响。EGFR基因突变具有癌变作用,可能影响到非小细胞肺癌预后、化疗和靶向药物的疗效。     

中国人群非小细胞肺癌表皮生长因子受体基因突变的分析

目的探讨中国人群非小细胞肺癌(NSCLC)患者表皮生长因子受体(EGFR)基因的突变情况。方法经病理确诊的254例NSCLC患者,采用聚合酶链反应(PCR)扩增、突变富集PCR和基因测序的方法检测EGFR第18、19、20和21外显子的突变情况。结果 204例NSCLC患者EGFR突变率为29.1%。EGFR在不同NSCLC类型中的突变率存在差异(P<0.001)。结论中国人群NSCLC患者的EGFR突变率基本与之前的报道相符,与西方人群的比例无明显差异。     

表皮生长因子受体在肺癌组织中的表达

目的　探讨肺癌组织中表皮生长因子受体 (EGFR)的表达水平及其临床意义。方法　采用免疫组化ABC法检测 3 9例肺良性疾病、95例原发性肺癌及癌旁肺组织中EGFR的表达水平。结果　非小细胞肺癌 (NSCLC)组织EGFR表达阳性率为 87.9% ( 80 / 91) ,肺良性病变肺组织为 10 .3 % ( 4/3 9) ,4例小细胞肺癌 (SCLC)无EGFR表达。在NSCLC中 ,距癌组织 3cm以内癌旁肺组织EGFR阳性率为6 3 .7% ( 5 8/ 91) ,6cm以远正常肺组织为 12 .1% ( 11/ 91)。结论　肺癌组织EGFR表达水平显著高于良性疾病肺组织 ,检测EGFR表达有助于肺部良恶性疾患的鉴别诊断。     

CT影像组学特征预测晚期肺腺癌EGFR基因突变的价值研究

目的:探究影像组学特征对于晚期肺腺癌EGFR基因突变状态的预测价值.方法:回顾性分析2013年04月至2019年09月期间青岛大学附属医院收治的339例晚期肺腺癌患者,其中237例作为训练组,102例作为验证组,从患者胸部CT动脉期及静脉期图像中各提取396个影像组学特征.依次应用mRMR和LASSO在训练组进行特征筛...     

表皮生长因子、雄激素受体和表皮生长因子受体在肝癌组织中的表达及影响因素分析

目的探讨肝癌患者肝癌组织中的表皮生长因子(EGF)、雄激素受体(AR)、表皮生长因子受体(EGFR)的表达情况及临床意义。方法采用免疫组织化学染色法检测EGF、AR、EGFR在90例肝癌患者的肝癌组织和90例非肝癌患者的非肝癌组织中的表达情况,比较不同临床特征肝癌患者肝癌组织中EGF、AR、EGFR的表达情况,分析肝癌患者肝癌组织中EGF、AR、EGFR表达的影响因素。结果肝癌组织中的EGF、AR、EGFR的阳性表达率均明显高于非肝癌组织,差异均有统计学意义(P﹤0.01)。有肝炎史、Ⅲ+Ⅳ期、中低分化、有淋巴结转移的肝癌患者肝癌组织中EGF、AR、EGFR的阳性表达率均高于无肝炎史、Ⅰ+Ⅱ期、高分化、无淋巴结转移的肝癌患者,差异均有统计学意义(P﹤0.05);不同年龄、性别、肿瘤直径的肝癌患者肝癌组织中EGF、AR、EGFR的阳性表达率比较,差异均无统计学意义(P﹥0.05)。Logistic回归分析结果显示,有淋巴结转移、TNM分期为Ⅲ+Ⅳ期是肝癌患者肝癌组织中EGF、AR、EGFR表达的独立危险因素。结论EGF、AR、EGFR在肝癌患者的肝癌组织中呈高表达,且其表达与肝癌患者的淋巴结转移情况和TNM分期密切相关。     

Osimertinib in patients with epidermal growth factor receptor T790M advanced non‐small cell lung cancer selected using cytology samples

Osimertinib is a potent, irreversible epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) selective for EGFR‑TKI sensitizing (EGFRm) and T790M resistance mutations. The primary objective of the cytology cohort in the AURA study was to investigate safety and efficacy of osimertinib in pretreated Japanese patients with EGFR T790M mutation‐positive non‐small cell lung cancer (NSCLC), with screening EGFR T790M mutation status determined from cytology samples. The cytology cohort was included in the Phase I dose expansion component of the AURA study. Patients were enrolled based on a positive result of T790M by using cytology samples, and received osimertinib 80 mg in tablet form once daily until disease progression or until clinical benefit was no longer observed at the discretion of the investigator. Primary endpoint for efficacy was objective response rate (ORR) by investigator assessment. Twenty‐eight Japanese patients were enrolled into the cytology cohort. At data cut‐off (February 1, 2016), 12 (43%) were on treatment. Investigator‐assessed ORR was 75% (95% confidence interval [CI] 55, 89) and median duration of response was 9.7 months (95% CI 3.8, not calculable [NC]). Median progression‐free survival was 8.3 months (95% CI 4.2, NC) and disease control rate was 96% (95% CI 82, 100). The most common all‐causality adverse events were paronychia (46%), dry skin (46%), diarrhea (36%) and rash (36%). Osimertinib provided clinical benefit with a manageable safety profile in patients with pretreated EGFR T790M mutation‐positive NSCLC whose screening EGFR T790M mutation‐positive status was determined from cytology samples. (ClinicalTrials.gov number NCT01802632).     

Late breast metastasis from resected lung cancer diagnosed by epidermal growth factor receptor gene mutation

Primary lung cancer metastasizes to various organs, but rarely metastasizes to the breast. We report a case of breast metastasis from primary lung cancer, which was confirmed by the detection of the same epidermal growth factor receptor (EGFR) gene mutation.     

表皮生长因子受体突变:gefitinib和erlotinib治疗非小细胞肺癌的靶点研究进展

Gefitinib和erlotinib是表皮生长因子受体酪氨酸激酶抑制剂(EGFR-TKI)类药物,是目前治疗非小细胞肺癌(NSCLC)的热点,已在多个临床试验中证实,东亚人群、女性、无吸烟史和腺癌患者有效,进一步的研究揭示癌症病人EGFR酪氨酸激酶区突变与对EGFR-TKI的敏感性密切相关。这些突变包括框架缺失、点突变等多种类型。本文综述了EGFR突变的研究现状和进展。     

早期肺腺癌EGFR基因突变的相关因素研究

目的：探讨早期（cT1N0M0期）肺腺癌EGFR突变的临床、病理及高分辨率CT（HRCT）相关因素,为早期肺腺癌患者术后行EGFR基因检测提供参考。方法回顾性分析行手术切除且术后采用DNA直接测序法完成EGFR基因突变状态检测的82例cT1N0M0期肺腺癌患者的病历资料。采用卡方检验、t检验、秩和检验分析临床、病理学及HRCT特征在EGFR有效突变组与非有效突变组中的差异;相关因素的界值采用ROC曲线确定;采用Logistic回归分析探寻EGFR突变的独立危险因素。结果82例肺腺癌中发生EGFR基因有效突变53例,非有效突变（包括野生型、无效突变）29例。EGFR有效突变组与非有效突变组在性别（P=0.017）,年龄（P=0.005）,吸烟与否（P=0.004）,是否为乳头为主型（P=0.048）,病灶大小（P=0.019）的差异具有统计学意义。患者年龄≥60岁（OR=6.852,95% CI 1.985~23.652,P=0.002）为cT1N0M0期肺腺癌EGFR基因有效突变的独立危险因素。结论cT1N0M0期肺腺癌中女性、年龄≥60岁、无吸烟、病理亚型为乳头为主型和病灶≥1.6 cm者出现EGFR有效突变概率较大。对于具有这些因素的cT1N0M0期肺腺癌患者,可考虑推荐于术后行EGFR基因检测。     

Comprehensive epidermal growth factor receptor gene analysis from cytological specimens of non-small-cell lung cancers

Epidermal growth factor receptor (EGFR) gene mutations and increased copy numbers are considered as predictors of response to EGFR tyrosine kinase inhibitors (EGFR-TKI) in non-small-cell lung cancer (NSCLC). Lung cancer diagnosis is often based on cytology alone. However, almost all published data on EGFR gene analyses were obtained from biopsies. This study tested the feasibility of EGFR gene analyses on cytological specimens. Eighty-four cytological specimens from NSCLCs were prospectively analysed for EGFR gene mutation in exons 18-21 and EGFR gene copy numbers were evaluated by fluorescence in situ hybridisation (FISH). A FISH-positive result was defined according to the criteria by Cappuzzo et al established for biopsies of NSCLCs. Fluorescence in situ hybridisation results of cytological specimens were compared to the FISH results on matching biopsies (n=33). Initial diagnosis of NSCLC was solely based on cytology in 37 out of 84 (44.0%) patients. Out of 80 NSCLCs, 6 (7.5%) showed EGFR gene mutations. Out of 67 cancers, 45 (67.2%) were FISH positive on cytological specimens. Comparison of FISH showed a FISH-positive result in 21 out of 33 (63.6%) cytological specimens but in only 8 out of 33 (24.2%) matched biopsies. Epidermal growth factor receptor gene analyses are well applicable to cytological specimens. The high FISH-positive rate of NSCLC on cytological specimens contrasts with the low rate on biopsies when previously suggested criteria are used. New criteria for a positive EGFR FISH status to predict response to therapy with EGFR-TKI need to be defined for cytological specimens.     

Retracted: Genistein enhances the effect of epidermal growth factor receptor tyrosine kinase inhibitors and inhibits nuclear factor kappa B in nonsmall cell lung cancer cell lines

BACKGROUND:

Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR‐TKIs) have shown modest clinical benefit in patients with relapsed nonsmall cell lung cancer (NSCLC). Down‐regulation of Akt appears to correlate with the antitumor activity of EGFR‐TKIs. Akt activates nuclear factor kappa B (NF‐κB), which transcribes genes important for cell survival, invasion, and metastasis. The authors hypothesized that genistein, through the inhibition of NF‐κB, could enhance the activity of EGFR‐TKIs in NSCLCs.

METHODS:

Three NSCLC cell lines with various EGFR mutation status and sensitivities to EGFR‐TKIs were selected: H3255 (L858R), H1650 (del E746‐A750), and H1781 (wild‐type EGFR). Cells were treated with erlotinib, gefitinib, genistein, or the combination of each of the EGFR‐TKIs with genistein. Cell survival and apoptosis were assessed, and expression levels of EGFR, pAkt, cyclooxygenase‐2 (COX‐2), E‐cadherin, prostaglandin E₂ (PGE₂), and NF‐κB were measured.

RESULTS:

Both EGFR‐TKIs demonstrated growth inhibition and apoptosis in each of the cell lines, but H1650 and H1781 were much less sensitive. Genistein demonstrated some antitumor activity in all cell lines, but enhanced growth inhibition and apoptosis when combined with the EGFR‐TKIs in each of the cell lines. Both combinations down‐regulated NF‐κB significantly more than either agent alone in H3255. In addition, the combinations reduced the expression of EGFR, pAkt, COX‐2, and PGE_2, consistent with inactivation of NF‐κB.

CONCLUSIONS:

The authors concluded that genistein enhances the antitumor effects of EGFR‐TKIs in 3 separate NSCLC cell lines. This enhanced activity is in part because of greater reduction in the DNA‐binding activity of NF‐κB when EGFR‐TKIs were combined with genistein. Cancer 2009. © 2009 American Cancer Society.