人工神经网络分析预测非小细胞肺癌患者EGFR基因突变的模型建立及其关联因素分析

目的应用人工神经网络法(ANN)建立预测非小细胞肺癌(NSCLC)患者EGFR基因突变模型及分析其关联因素,为NSCLC治疗提供数据。方法采用扩增阻滞突变系统检测434例NSCLC患者样本的EGFR基因外显子19缺失、外显子20 T790M突变、外显子21 L858R突变,应用ANN建立NSCLC患者EGFR基因突变预测模型及分析其关联因素。结果显示434例NSCLC患者EGFR基因外显子19、20、21总突变率为42.6%,其中腺癌EGFR基因突变率明显高于鳞癌、大细胞癌,女性突变率明显高于男性。最终ANN预测模型变量包括吸烟、吸烟指数、病理类型、胸水CEA、性别、血液CEA,该模型曲线下面积、灵敏度、特异度分别为0.806、64.00%、73.50%。进一步分析显示较高胸水CEA、腺癌、吸烟人群、高血液CEA水平、高吸烟指数、女性肺癌患者更易发生EGFR突变。结论 NSCLC患者EGFR基因突变率较高;本研究建立了ANN预测NSCLC患者EGFR突变预测模型,具有较好的诊断效能。     

ERCC1与TS在非小细胞肺癌中的表达及与铂类化疗敏感性的关系

目的 通过对非小细胞肺癌(NSCLC)组织与癌旁组织中切除修复交叉互补基因1(ERCC1)、胸苷酸合成酶(TS)的检测,探讨其表达与NSCLC临床特征及预后的关系,为NSCLC个体化治疗提供实验依据.方法 采用免疫组化方法检测50例NSCLC患者术后癌组织和癌旁组织标本中ERCC1、TS蛋白的表达水平,探讨ERCC1、TS的表达与NSCLC患者总生存期(OS)、疾病进展时间(TTP)及中位OS、中位TTP之间的关系.结果 (1)ERCC1、TS在NSCLC患者癌组织与癌旁组织中的阳性表达率比较,差异具有统计学意义(64.00％ vs 20.00％,x2=19.87,P＜0.01;48.00％ vs24.00％,x2=6.25,P＜0.05).(2)接受术后铂类方案化疗并随访,ERCC1阴性表达者中位OS明显长于阳性表达者(19.10个月vs 10.00个月,x2=8.133,P=0.002),中位TTP亦明显长于阳性表达者(15.30个月vs 9.00个月,x2=7.410,P=0.003).TS阴性表达者的中位OS(17.80个月vs11.00个月,x2=7.001,P=0.008)、中位TTP(11.40个月vs 6.80个月,x2=5.884,P=0.026)均明显长于TS阳性表达者.结论 ERCC1、TS蛋白可能成为NSCLC患者对铂类药物敏感性的预测因子;二者联合检测有助于NSCLC患者个体化治疗方案的选择.     

ERCC1,p53和bcl-2表达与晚期非小细胞肺癌铂类化疗疗效的关系

目的研究核苷酸切除修复交叉互补基因1(ERCC1),抑癌基因p53(p53)和B细胞淋巴瘤因子2(bcl-2)基因的表达水平与晚期非小细胞肺癌(NSCLC)患者铂类化疗疗效的关系。方法收集晚期NSCLC患者的肿瘤组织并制备组织芯片,进行ERCC1,p53和bcl-2基因的免疫组织化学染色,检测其在NSCLC组织中的表达情况;同时采集患者外周血检测其血清中ERCC1,p53和bcl-2蛋白的表达情况。根据RECIST肿瘤化疗疗效的评价标准评价患者的疗效,分析影响NSCLC患者铂类化疗疗效的因素及3种基因的表达情况和疗效的关系。结果 ERCC1阴性表达和阳性表达时的化疗有效率分别为55.81%和25.58%(P<0.01);bcl-2阴性表达和阳性表达时的化疗有效率分别为45.28%和25%(P<0.05);p53阴性表达和阳性表达时的化疗有效率分别为53.85%和29.79%(P<0.05)。以ERCC1阴性,同时bcl-2阴性和p53阳性表达的患者人数为最多,与其他各组相比差异有统计学意义(P<0.05),而其他各组人数差异无统计学意义(P>0.05);以ERCC1阴性表达同时bcl-2阳性表达和p53阴性表达的患者采用铂类化疗的有效率为最高,与其他情况相比差异有统计学意义(P<0.05);而ERCC1,bcl-2和p53基因均为阳性表达时的化疗有效率最差,与其他情况相比差异有统计学意义(P<0.01)。结论 ERCC1,p53和bcl-2基因的表达水平可以作为预测NSCLC患者铂类化疗疗效和预后的指标。     

非小细胞肺癌EGFR基因突变与扩增的比较及其与血清CEA水平的关系

目的比较分析非小细胞肺癌(NSCLC)表皮生长因子受体(EGFR)基因突变与扩增的关系,并探讨其与血清癌胚抗原(CEA)水平有无相关性。方法对270例确诊非小细胞肺癌的肺组织标本(包括手术切除及经纤支镜活检取得)用实时荧光定量PCR法技术检测EGFR基因突变状态,用荧光原位杂交技术检测EGFR基因的扩增情况。治疗前抽取患者静脉血,用化学发光法检测血清CEA水平。结果 270例NSCLC中EGFR基因突变率为31.11%,EGFR基因扩增率为20%,基因突变并扩增的占10.74%。基因突变组、基因扩增组、基因突变并扩增组和基因无突变无扩增组血清CEA平均水平分另为[3.03(1.68-6.22)]ng/mL、[3.19(1.8-17.17)]ng/mL、[3.39(1.85-20.87)]ng/mL和[2.54(1.5-4.62)]ng/mL。基因突变组与基因扩增组、基因突变组与基因无突变无扩增组血清CEA比较无显著性差异(P>0.05)。基因扩增组与基因无突变无扩增组、基因突变并扩增组与基因无突变无扩增组血清CEA比较有显著性差异(P<0.05)。EGFR基因突变、基因扩增及基因突变并扩增与血清CEA水平有明显相关性。结论在NSCLC中EGFR基因突变率大于扩增率,其机制有待进一步阐明。EGFR基因与血清CEA水平有明显相关性。血清CEA水平有可能成为指导非小细胞肺癌EGFR靶向治疗的指标。     

扩增阻滞突变系统检测晚期非小细胞肺癌患者外周血游离DNA中EGFR基因突变

目的探究外周血游离DNA(cf DNA)检测非小细胞肺癌(NSCLC)患者表皮生长因子受体(EGFR)基因突变的可行性。方法收集2013年7月-2014年1月湖北省肿瘤医院收治50例确诊为晚期NSCLC患者的肿瘤组织及配对的外周血样本,分别提取肿瘤组织DNA及cf DNA,采用基于实时荧光定量PCR的扩增阻滞突变系统(ARMS)检测两类样本中EGFR基因突变。结果以肿瘤组织的结果为准,cf DNA中检出突变的特异性为97.2%(35/36),敏感度为78.6%(11/14),一致性为92.0%(46/50),且具有和肿瘤组织相同的EGFR基因突变类型。结论 cf DNA和肿瘤组织的EGFR基因突变类型相同,一致性、特异性和敏感度较高,对于晚期难以获得组织的NSCLC患者,外周血可代替肿瘤组织应用于临床EGFR基因突变检测。     

DNA修复基因在基于铂类药物化疗的非小细胞肺鳞癌患者中的预后价值

目的了解DNA修复基因在接受以铂类药物为基础化疗的非小细胞肺癌(NSCLC)患者中不同病理类型的预后价值。 方法应用免疫组织化学技术检测121例NSCLC铂类药物化疗患者石蜡包埋病灶组织中多聚ADP-核糖聚合酶基因1(PARP1),切除修复交叉互补基因1(ERCC1),错配修复同源型2基因(MSH2),乳腺癌易感基因1(BRCA1)表达状态。分析NSCLC患者DNA修复基因的表达与临床病理特征之间的关系。并通过生存分析判断DNA修复基因的表达在不同病理类型中NSCLC化疗患者中的预后价值及是否为独立的预后指标。 结果ERCC1、PARP1、BRCA1、MSH2在非小细胞肺癌的表达均未显示与患者的性别、年龄、吸烟指数、临床TNM分期的相关性(P均>0.05)。在NSCLC腺癌组中ERCC1、PARP1、BRCA1、MSH2均不是判断预后的独立因素(P均>0.05)。鳞癌组中ERCC1、PARP1是预后判断独立因素(P=0.019,0.031)。 结论ERCC1、PARP1是基于铂类药物化疗的非小细胞肺鳞癌患者独立的预后指标。     

非小细胞肺癌表皮生长因子及间变性淋巴瘤激酶基因检测及临床病理特征

目的研究汉族人群中表皮生长因子(epidermal growth factor receptor, EGFR)基因突变和间变性淋巴瘤激酶(anaplastic lymphoma kinase, ALK)基因融合在非小细胞肺癌(non-small cell lung cancer, NSCLC)患者中的阳性率及其与临床病理特征的关系。方法收集本院非小细胞肺癌临床手术患者522例,通过ARMS-PCR方法检测NSCLC标本中EGFR基因突变和ALK基因的常见基因融合变异,分析其与患者的病理学分型、性别和年龄等临床指标的相关性。结果对共522例NSCLC手术标本检测了EGFR基因突变,并同时对其中149例标本检测了ALK基因的常见基因融合变异。EGFR基因与ALK融合基因突变阳性率分别为42.91%(224/522)与7.38%(11/149)。EGFR基因突变多发生于女性和腺癌中。另外在149例同时检测了EGFR基因突变和ALK基因融合的标本中,有1例(0.67%,1/149)检测到了EGFR基因突变合并ALK基因融合的罕见驱动基因双突变。结论在汉族人群非小细胞肺癌患者中,EGFR基因突变与患者的性别及病理学分型等临床指标存在明显相关性。ALK基因融合及EGFR、ALK双突变共存型基因突变率虽然较低,但其意义不容忽视,临床医生应给予充分重视。     

武汉地区非小细胞肺癌EGFR基因突变相关性研究

目的调查武汉地区非小细胞肺癌(NSCLC)患者表皮生长因子受体(EGFR)基因型分布特点,探究肺癌组织EGFR基因突变与患者吸烟习惯、肿瘤病理学类型、肿瘤分化程度以及淋巴结转移与否的相关性。方法收集185例NSCLC患者石蜡组织切片,采用常规聚合酶链反应(PCR)方法检测EGFR基因18、19、20、21四个外显子,DNA测序分析确定EGFR基因突变类型。结果 185例NSCLC患者中,男性EGFR突变率为7.3%,明显低于女性的17.8%,差异有统计学意义(P0.05);吸烟患者FGFR基因突变率为7.7%,明显低于不吸烟者的20.0%,差异有统计学意义(P0.01),其中腺癌EGFR突变率为15.3%(18/118),腺鳞癌突变率为10.0%(3/30),鳞癌突变率为5.4%(2/37);共检测出7种类型突变,分别为Gln787Gln、Leu858Arg、E746-A750del、S752-I759del、A750-I759del、Gly719Ser、Ser768Ile。结论武汉地区NSCLC EGFR基因的突变形式主要为点突变及缺失突变。EGFR基因突变与患者性别有关,与肿瘤病理学类型、肿瘤分化程度和淋巴结转移与否无明显关系。     

衢州地区非小细胞肺癌EGFR基因突变分析

目的探讨衢州地区非小细胞肺癌(non-small cell lung cancer,NSCLC)患者表皮生长因子受体(epidermal growth factor receptor,EGFR)基因突变特点的相关性。方法选取2017年1月至2018年2月衢州市人民医院收治的106例NSCLC患者的石蜡包埋组织,采用PCR-荧光探针法检测EGFR基因第18～21号外显子基因突变情况。结果 106例NSCLC患者总突变率为43.40%,第18、19、20、21号外显子突变率分别占突变总数的2.17%,41.31%,4.34%,52.18%,女性EGFR基因的突变率高于男性,差异有统计学意义(χ~2=5.52,P=0.02),无吸烟史患者高于有吸烟史患者,差异有统计学意义(χ~2=4.76,P=0.03),腺癌患者高于鳞癌患者,差异有统计学意义(χ~2=10.59,P=0.01),EGFR基因的突变率与NSCLC患者的年龄无相关性(χ~2=0.65,P=0.42)。结论衢州地区NSCLC患者EGFR基因突变以19号外显子的缺失和21号外显子的点突变为主,女性、无吸烟史及腺癌的NSCLC患者EGFR基因突变率较高,可接受以EGFR为靶点的小分子酪氨酸激酶抑制剂治疗。     

结直肠癌k-ras突变与ERCC1mRNA表达相关性研究

目的:探讨结直肠癌k-ras基因突变与ERCC1mRNA表达相关性,为结直肠癌化疗提供理论依据.方法选择2012年1月~2014年6月间我院送检的结直肠癌病例92例,应用直接测序法检测肿瘤组织k-ras基因突变情况,应用RT-PCR相对定量分检测肿瘤组织ERCC1mRNA表达水平.结果:92例结直肠癌患者肿瘤组织中,共有29例发生了k-ras突变,突变发生率为31.5%.k-ras突变型患者ERCC1mRNA表达水平显著高于k-ras野生型患者(P<0.05).不同肿瘤长度、浸润深度、分化程度、临床分期及淋巴结转移患者ERCC1mRNA表达水平(△CT)无统计学差异(P>0.05).Pearson相关分析显示ERCC1mRNA表达水平与肿瘤长度、浸润深度、分化程度、临床分期及淋巴结转移无相关性(P>0.05),与k-ras突变发生呈正相关(r=0.667,P<0.05).结论:结直肠癌k-ras突变与ERCC1mRNA表达密切相关,二者可能与结直肠癌化疗联合西妥昔单抗治疗耐药有一定关系.     

185例华南地区非小细胞肺癌EGFR基因突变分析

目的探讨华南地区非小细胞肺癌（NSCLC）表皮生长因子受体（EGFR）基因突变特点及与临床特征的关系。方法收集本院185例NSCLC肿瘤组织，分别提取DNA，采用荧光PCR法扩增EGFR基因第18、19、20、21号外显子，对扩增片段进行DNA正反向测序并分析。结果185例NSCLC中，62例（33．5％）EGFR基因突变，其中18、19、20、21外显子突变分别为2例、41例、5例、14例；共见突变类型16种，热点突变类型为19外显子DelL747→P752（P753S）（构成比8．1％）、DelE746→A750（构成比45．1％）和21外显子L858R（构成比22．6％）；其中4例19外显子突变正、反向测序结果不一致。见20外显子2361G→A沉默突变（28．1％）；女性突变率显著高于男性（46．2％vs24．3％，X2=9．670，P=0．002）。不吸烟者突变率高于吸烟者（41．4％vs17．1％，X2=7．380，P=0．007）。腺癌患者突变率高于鳞癌患者（38．3％vs6．3％，X2=6．426，P=0．011）。临床Ⅲ期患者突变率显著低于临床Ⅱ期、Ⅳ期患者（10．8％vs53．8％，X2=8．026，P=0．003；10．8％vs41．3％，X2=9．518，P=0．002）。同时，未发现EGFR基因突变率与年龄相关。结论华南地区NSCLC患者EGFR基因突变以19、21外显子突变为主。突变率以女性、不吸烟、腺癌者较高。     

Association of MDR1 and ERCC1 polymorphisms with response and toxicity to cisplatin-based chemotherapy in non-small-cell lung cancer patients

Among the cancer patient population, resistance to therapy is a major cause for therapeutic failure and for human sufferings, especially for the cancer with poor prognosis. Therefore, finding factors that contribute to drug resistance is a major research interest. In this study, we have investigated whether polymorphisms in genes that control import/export of drugs (MDR1) and that repair DNA adducts (ERCC1) are involved with drug resistance in non-small cell lung cancer (NSCLC) patients. We have recruited 95 patients with advanced NSCLC (stages IIIB-IV) who were specifically treated with platinum-based chemotherapy. We used the ligase detection reactions assay (LDR) to detect polymorphisms in ERCC1 118C/T, and MDR1 2677T/A, E1/-129T/C, and C3435T in peripheral blood lymphocytes from the patients. The haplotype of MDR1 gene single nucleotide polymorphisms (SNPs) were analyzed using the SHEsis software platform on line. We found that none of the single polymorphisms was associated with treatment response or related toxicity. However, patients carrying at least one variant MDR1 2677 T allele was associated with a significantly increased risk of drug resistance (OR=1.844, 95% CI=1.01-3.53, P=0.04) but also with a significantly increased risk of gastrointestinal toxicity (P=0.03) but not hemato-, hepato- or nephro-toxicities. Moreover, we analyzed the haplotypes of the three polymorphisms in MDR1. The patients harboring the E1/-129T-2677T-3435C haplotype had a significantly better response to chemotherapy compared with those having the other haplotypes (P=0.02, 95% CI=1.20-25.87), and a marginally significant association with increased risk of gastrointestinal toxicity (P=0.02, 95% CI=1.15-3.88). Our results suggested that gene polymorphisms in MDR1G2677T/A may be a predictive marker of platinum-based treatment response and of secondary effects, especially gastrointestinal toxicity for advanced NSCLC patients.     

Estimating quality adjusted progression free survival of first-line treatments for EGFR mutation positive non small cell lung cancer patients in The Netherlands

ABSTRACT: BACKGROUND: Gefitinib, a tyrosine kinase inhibitor, is an effective treatment in advanced non-small cell lung cancer (NSCLC) patients with an activating mutation in the epidermal growth factor receptor (EGFR). Randomised clinical trials showed a benefit in progression free survival for gefitinib versus doublet chemotherapy regimens in patients with an activated EGFR mutation (EGFR M+). From a patient perspective, progression free survival is important, but so is health-related quality of life. Therefore, this analysis evaluates the Quality Adjusted progression free survival of gefitinib versus three relevant doublet chemotherapies (gemcitabine/cisplatin (Gem/Cis); pemetrexed/cisplatin (Pem/Cis); paclitaxel/carboplatin (Pac/Carb)) in a Dutch health care setting in patients with EGFR M + stage IIIB/IV NSCLC. This study uses progression free survival rather than overall survival for its time frame in order to better compare the treatments and to account for the influence that subsequent treatment lines would have on overall survival analysis. METHODS: Mean progression free survival for Pac/Carb was obtained by extrapolating the median progression free survival as reported in the Iressa-Pan-Asia Study (IPASS). Data from a network meta-analysis was used to estimate the mean progression free survival for therapies of interest relative to Pac/Carb. Adjustment for health-related quality of life was done by incorporating utilities for the Dutch population, obtained by converting FACT-L data (from IPASS) to utility values and multiplying these with the mean progression free survival for each treatment arm to determine the Quality Adjusted progression free survival. Probabilistic sensitivity analysis was carried out to determine 95% credibility intervals. RESULTS: The Quality Adjusted progression free survival (PFS) (mean, (95% credibility interval)) was 5.2 months (4.5; 5.8) for Gem/Cis, 5.3 months (4.6; 6.1) for Pem/Cis; 4.9 months (4.4; 5.5) for Pac/Carb and 8.3 (7.0; 9.9) for gefitinib. CONCLUSIONS: In the Dutch health care setting, the previously established progression free survival benefit of first-line gefitinib in advanced NSCLC EGFR M + patients in comparison to standard doublet chemotherapy is further supported by the Quality Adjusted PFS, which takes into account the additional health-related quality of life benefits of gefitinib over doublet chemotherapy.     

Combined Treatment with Epimedium koreanum Nakai Extract and Gefitinib Overcomes Drug Resistance Caused by T790M Mutation in Non-Small Cell Lung Cancer Cells

Although the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors, such as gefitinib, have shown promising therapeutic efficacy in nonsmall cell lung cancer (NSCLC) patients harboring EGFR activating mutation, development of acquired resistance is almost inevitable. We investigated whether the addition of Epimedium koreanum Nakai extract (EEF) to gefitinib could overcome the resistance of NSCLC cells to gefitinib. In our study, the growth inhibitory effects of cotreatment differed between mutant EGFR and wild type EGFR. A synergistic antiproliferative effect was observed in the combined treatments in H1975 and PC-9GR cells carrying T790M EGFR. In addition, the cotreatment exhibited a much greater inhibition than either agent alone on the following metastatic processes: (a) invasion, (b) wound healing, and (c) tubule formation by endothelial cells. The phosphorylations of EGFR family (EGFR, HER-2, and HER-3) and EGFR downstream PI3K/Akt/mTOR pathway in H1975 and PC-9/GR cells were also attanuated, whereas EEF or gefitinib alone had no obvious effects. Similarly, the combination effectively suppressed tumor growth and increased mice survival in PC-9GR xenografts. The results indicate that the addition of EEF to gefitinib is a promising strategy to overcome T790M-mediated drug resistance.     

Body Mass Index,Weight Loss,and Mortality Risk in Advanced-Stage Non-Small Cell Lung Cancer Patients: A Focus on EGFR Mutation

Body mass index (BMI) influences the prognosis of patients with non-small cell lung cancer (NSCLC), including both early-stage and late-stage NSCLC patients that are undergoing chemotherapies. However, earlier research on the relationship between BMI and survival in patients taking epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) yielded contradictory results. These publications either had a limited number of patients or were getting TKIs in various lines of therapy, which might explain why the outcomes were contradictory. As a result, we undertook retrospective study to examine the effect of BMI on survival outcomes in patients with advanced EGFR mutant NSCLC receiving first-line EGFR-TKIs. We also compared the findings to those with wild-type EGFR. Between November 2010 and March 2014, 513 patients with advanced NSCLC were enrolled in the study. According to the adjusted BMI cut-off point for Asia, 35 out of 513 (6.8%) patients were underweight (BMI < 18.5 kg/m²), whereas 197 (38.4%) were overweight (BMI > 24 kg/m²). Overweight patients with wild-type EGFR exhibited longer progression-free survival (4.6 vs. 2.1 months, p = 0.003) and overall survival (OS) (8.9 vs. 4.3 months, p = 0.003) than underweight patients. Overweight patients with EGFR mutations had a longer OS than normal-weight patients (23.0 vs. 20.2 months, p = 0.025). Bodyweight reduction was related to a shorter OS in both the mutant EGFR patients (17.1 vs. 30.5 months, p < 0.001) and the wild-type EGFR patients (7.8 vs. 18.7 months, p < 0.001). In conclusion, advanced stages NSCLC patients with a lower BMI and early weight loss had a worse outcome that was independent of EGFR mutation status.     

New therapies for the treatment of advanced non-small cell lung cancer: inhibitors of the epidermal growth factor receptor and angiogenesis

The recently developed 'targeted' therapies, epidermal growth factor receptor (EGFR) inhibitors and angiogenesis inhibitors, target specific tumour characteristics. EGFR inhibitors, such as gefitinib and erlotinib, can lead to remission, particularly in non-small cell lung cancer (NSCLC) with specific EGFR mutations. These mutations occur more frequently in Asians, women, non-smokers and those with adenocarcinomas. Other mutations in EGFR and K-ras genes lead to resistance. EGFR inhibitors offered no benefit to untreated patients with advanced NSCLC. In previously treated patients, however, erlotinib increased survival by 2 months. Optimal patient selection criteria for EGFR inhibitor therapy is still under investigation. The angiogenesis inhibitor bevacizumab is an antibody that targets vascular endothelial growth factor receptor. The addition of bevacizumab to chemotherapy increased median survival by 2 months when given as first-line therapy for advanced NSCLC. The combination of EGFR and angiogenesis inhibitors is a rational anticancer treatment and is being studied. These new therapies are expected to help improve and individualize the treatment of advanced NSCLC.     

A newly detected mutation of the RET protooncogene in exon 8 as a cause of multiple endocrine neoplasia type 2A

Multiple endocrine neoplasia type 2A (MEN2A) is a syndrome of familial neoplasias characterized by medullary thyroid carcinoma (MTC), pheochromocytoma and hyperplasia of the parathyroid glands. RET protooncogene mutations are responsible for MEN 2A. Mutations in exons 10 or 11 have been identified in more than 96% of patients with MEN 2A. We herein report for the first time a patient with MEN 2A harboring a mutation (Gly(533)Cys) in exon 8. A 66-year old male patient was referred to our department for bilateral adrenal nodules. The patient's family history was remarkable in that his mother had pheochromocytoma. Biochemical evaluation and findings of the magnetic resonance imaging of the adrenals were compatible with the diagnosis of bilateral pheochromocytomas. The patient underwent laparoscopic bilateral adrenalectomy and histological examination confirmed the preoperative diagnosis of pheochromocytoma. Absence of phenotypic characteristics of VHL or NF1 and elevated calcitonin levels both basal and post pentagastrin stimulation, raised the possibility of MEN 2A syndrome. Total thyroidectomy was performed and histological examination showed the presence of MTC. Direct sequencing of exon 8 from the patient's genomic DNA revealed the mutation c.1,597G-->T (Gly533Cys). Although this missense point mutation has been associated with familial MTC (FMTC), to the best of our knowledge mutations in exon 8 have not previously been identified in patients with MEN 2A. In conclusion, in patients with clinical suspicion of MEN 2A syndrome, analysis of RET exon 8 should be considered when the routine evaluation of MEN 2A-associated mutations is negative. Furthermore, patients with FMTC and exon 8 mutations should also be screened for pheochromocytoma.     

肿瘤坏死因子-α-转化酶和EGFR在非小细胞肺癌转移中的作用研究

目的探讨非小细胞肺癌（NSCLC）病理组织中肿瘤坏死因子-α-转化酶（TACE）和EGFR在原发灶和转移灶中的表达及其与患者预后的关系。方法应用液相芯片技术、RT-PCR、WesternBlot等方法测定57例NSCLC和14例肺部良性病变病理切片中膜结合肿瘤坏死因子（M—TNF）、TACE、EGFR的水平,对比分析TACE、EGFR在NSCLC患者和正常人之间以及NSCLC原发灶和转移病灶的表达。结果57例NSCLC中M—TNF和TACE的异常表达率分别为66．67％和64．91％,EGFR的阳性表达率为77．19％;14例肺部良性病变均未见TACE的过度表达：TACE和EGFR在NSCLC转移灶中的表达明显高于原发灶,并与预后成正相关。结论检测TACE和EGFR在NSCLC中的表达变化是判断恶性肿瘤程度、浸润转移的有效参考指标,TACE和EGFR的异常表达可能影响NSCLC患者的预后。