表皮生长因子受体蛋白酪氨酸激酶的表达、纯化及活性测定

目的:采用原核表达体系对表皮生长因子受体(epidermal growth factor receptor,EGFR)受体型酪氨酸激酶(recep-tor tyrosine kinase,RTK)进行体外表达、纯化及活性鉴定.方法:以包含EGFR cDNA的pRK5质粒为模板,PCR选择扩增编码EGFR-RTK的cDNA片段,插入pQE30质粒后转染大肠杆菌M15.IPTG诱导表达融合蛋白,包涵体蛋白经复性后亲和层析法纯化,ELISA方法测定蛋白活性.结果:成功地将933 bp的EGFR-RTK cDNA片段插入载体pQE30中,构建了表达载体pQE30-RTK.经诱导在原核表达系统中以包涵体形式高效表达了相对分子质量为37 000的EGFR-RTK融合蛋白,表达量约占菌体总蛋白的65.2%.复性、纯化后的EGFR-RTK蛋白经ELISA检测,结果发现随着加入蛋白量的增加,酶促反应产物磷酸化酪氨酸的量也逐渐增加,两者具有线性关系.结论:本实验成功地利用原核表达系统表达了具有生物学活性的EGFR-RTK,较传统的昆虫细胞表达系统更为简便、经济.     

The epidermal growth factor receptor-tyrosine kinase inhibitor era has changed the causes of death of patients with advanced non-small-cell lung cancer

BackgroundEpidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are effective against tumor EGFR-mutated non-small cell lung cancer (NSCLC). Patients with the tumor EGFR-activating mutation (EGFRmu) had superior survival, compared to patients with EGFR wild-type tumors (EGFRwt). Many patients with the EGFRmu have had disease progression with EGFR-TKI treatment because of central nervous system (CNS) metastases. The objective of this retrospective study was to compare the causes of death in patients with a known tumor EGFR mutation status who had been treated with EGFR-TKIs.MethodsWe retrospectively reviewed the chart records of our patients with advanced NSCLC who had received diagnosis, treatment, and supportive and hospice care in our hospital between July 2005 and June 2010. The tumor EGFR mutation status was analyzed by using a DNA sequence method. All enrolled patients had a documented cause of death.ResultsNinety-four patients had documented tumor EGFR data, had received EGFR-TKI treatment (either erlotinib or gefitinib), and were with or without previous or salvage systemic chemotherapy. Of the 94 patients, 36 patients had EGFRwt and 58 patients had EGFRmu. The overall patient survival after starting EGFR-TKI treatment was significantly longer in the EGFRmu patients (median 17.2 months) than in the EGFRwt patients (median 11.6 months; p = 0.0058). Twenty-nine patients died of CNS metastases and 65 died of organ failure (other than the CNS). Patients who died of CNS metastases had undergone EGFR-TKI treatment significantly longer than patients who died of other organ failure (median, 8 months vs. 1.9 months; p = 0.0003) with a hazard ratio of 2.308 [95% confidence interval (C.I.), 1.452–3.668; p = 0.0004]. A significantly higher proportion of EGFRmu patients (26 of 58 patients; 44.8%) than EGFRwt patients (3 of 36 patients; 8.3%) (p < 0.001) died of CNS metastases.ConclusionThe EGFRmu NSCLC patients survived longer and had a significantly higher probability of mortality due to CNS metastases, compared to the EGFRwt patients. This change in the causes of death was noted after the era of EGFR-TKI treatment, and will have an important impact on the strategies and management of supportive and hospice care for patients.     

Expression of epidermal growth factor and its receptor in gestational trophoblastic diseases

Epidermal growth factor (EGF ) and itsreceptor (EGFR) play a crucial role in thefunctional control of the placenta trophoblastcells,and it was in the high attention of thedisorder of EGF/ EGFR autocrine and paracrinesystem in various malignant tumors. EGF andEGFR expression in gestational trophoblasticdisease (GTD) were detected in our study.MATERIALSAND METHODSMaterials　The in- patient biopsy of GTD wasrandomly chosen from the department of theGynecology of the First Hospi…     

表皮生长因子受体酪氨酸激酶抑制剂高通量筛选模型的建立

目的:建立表皮生长因子受体(epidermal growth factor receptor,EGFR)酪氨酸激酶(receptor tyrosine kinase,RTK)抑制剂的高通量筛选模型。方法:通过基因工程技术表达EGFR-RTK,ELISA法验证其生物学活性;应用表面等离子共振原理筛选与激酶具有结合活性的化合物,ELISA法检测其生物学活性。结果:在原核表达系统中成功表达具有生物学活性的EGFR-RTK蛋白。将蛋白偶联至生物芯片,阳性化合物EI 188与EGFR酪氨酸激酶结合的Kd值为5.00×10-7mol.L-1,IC50为12.37μmol.L-1,与预期结果一致。应用该模型筛选31个待测化合物,发现了6个具有结合活性和酶抑制活性的EGFR-RTK抑制剂。结论:成功建立了基于表面等离子共振原理和ELISA法的高通量EGFR-RTK抑制剂的筛选模型,为发现新型酪氨酸激酶抑制剂奠定了基础。     

表皮生长因子受体和转化生长因子Ⅱ型受体在胃癌组织中的表达

目的观察表皮生长因子受体(EGFR)和转化生长因子Ⅱ型受体(TβRⅡ)在胃癌组织中的表达。方法采用SABC法对30例慢性浅表性胃炎、30例胃溃疡、30例胃癌标本进行表皮生长因子受体(GEFR)和转化生长因子Ⅱ型受体(TβRⅡ)检测。结果EGFR和TβRⅡ在慢性浅表性胃炎、胃溃疡、癌胃组织中的表达不同,癌胃组明显高于胃溃疡组和慢性浅表性胃炎组(P<0.01);EGFR和TβRⅡ表达与胃癌患者的年龄、性别、肿瘤的部位及大小无明显关系(P>0.05),两者均与临床分期有关,Ⅲ~Ⅳ期明显高于Ⅰ~Ⅱ期(P<0.0 5);同时TβRⅡ与EGFR在胃癌中的表达无显著性差异(P>0.0 5),两者共同表达符合率为93.3%。结论EGFR、TβRⅡ在胃癌中有过度表达,其表达与胃癌的进展、转移有关,与胃癌患者年龄、性别、肿瘤的部位及大小无关;同时二者在胃癌组织中有协同表达。     

钙黏蛋白与表皮生长因子受体酪氨酸激酶抑制剂治疗肝细胞癌敏感性的相关性

目的 探讨钙黏蛋白（E-cadherin）表达在表皮生长因子受体酪氨酸激酶抑制剂（EGFR-TKI）治疗肝细胞癌耐药形成中的作用。方法 选取常见的4种肝细胞癌细胞HepG₂、BEL-7404、SK-HEP-1和MHCC97,用蛋白质印迹法检测这4种肝癌细胞中E-cadherin的蛋白表达,MTT法检测E-cadherin的表达与肝癌细胞EGFR-TKI治疗抑制率的相关性。结果 4种肝癌细胞中HepG₂、BEL-7404 表达E-cadherin呈阳性并对EGFR-TKI治疗敏感,PD153035和吉非替尼两种EGFR-TKI的药物浓度与肝癌细胞HepG₂、BEL-7404的生存率之间存在相关性（P<0.05）;然而,肝癌细胞SK-HEP-1和MHCC97中E-cadherin表达阴性并对EGFR-TKI治疗耐药,PD153035和吉非替尼两种药物浓度与肝癌细胞MHCC97、SK-HEP-1的生存率之间不存在相关性（P>0.05）。另外,E-cadherin表达阴性细胞SK-HEP-1转染E-cadherin目的基因后与转入空载体的肝癌细胞相比,EGFR-TKI治疗的敏感性上调（P<0.05）。结论 E-cadherin在调节EGFR分子靶向治疗的敏感性方面起重要作用。     

Phase I trial of icotinib, a novel epidermal growth factor receptor tyrosine kinase inhibitor, in Chinese patients with non-small cell lung cancer

Background  The preclinical experiments and studies of congener drugs show icotinib, a new epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, can specifically bind to the tyrosine kinase domain of the EGFR, block the EGFR related signal, thereby inhibit the growth of tumor cell. The objective of this study was to investigate the safety, tolerability and dose-related biologic effects of icotinib in patients with non-small cell lung cancer (NSCLC) in a Chinese patient population.

Methods  This was an open-label, phase I, dose escalation, safety/tolerability trial of oral icotinib (100 to 400 mg), administered twice per day for 28-continuous-day cycles until disease progression or undue toxicity.

Results  Forty patients with stage IIIB (15%) or IV (85%) NSCLC were included in the study. They had mainly adenocarcinoma (85%), with a performance status (PS) of 0 (45%) or 1 (55%) and less than half the patients (45%) had histories of smoking and all were pretreated by at least one regimen of chemotherapy. Patients were assigned to three dose levels of 150 mg b.i.d, 200 mg b.i.d, or 125 mg t.i.d. The follow-up periods ranged from 5 to 80 weeks. Adverse events were found in 35% patients, most of which were mild and reversible. The adverse events mainly occurred in the first 4 weeks and included rash (25%), diarrhea, nausea and abdominal distention. One definite interstitial lung disease (ILD) was found in a patient in the dose of 200 mg b.i.d. According to an 8-week assessment, one (2.5%) patient receiving 150 mg gained complete response (CR) that persisted for 44 weeks, seven (17.50%) patients had partial remission (PR), and 18 (45%) patients had stable disease (SD). The objective response including CR+PR was 20%. The median time of progression-free survival for the 40 patients was 20 weeks (range: 12 to 32 weeks). The response was not affected by pathological type, history of smoking, or numbers of previous therapeutic regimens. No relationship between dose, response, adverse effect, or duration of the study was observed.

Conclusions  Icotinib, given as oral twice daily, showed favorable safety and tolerability. Mild and reversible rash, diarrhea, and nausea were the main adverse events. Antitumor activity was obvious at each dose in heavily pretreated patients. Pharmacodynamic evaluations and further phase II/III trials are in progress.

     

表皮细胞生长因子受体测定及在肠癌的表达

本文报道灵敏、准确的表皮细胞生长因子(EGF)受体~(125)碘结合测定法.检测30例肠癌、癌周及正常肠组织 EGF 受体的表达。肠癌、癌周、正常肠组织 EGF 结合量分别为8.21±2.60(n=10),4.35±1.38(n=10)和1.41±0.43(n=10)fmol/mg膜蛋白,差异非常显著(P<0.01).Scatchard 作图,~(125)I-hEGF 结合是一条直线,肠癌 EGF 受体 KD 值25～315 fmol(n=9).     

表皮生长因子受体和血管内皮生长因子在胃近端癌组织中的表达

目的检测表皮生长因子受体（EGFR）和血管内皮生长因子（VEGF）分别在胃贲门部和胃窦部癌组织中的表达情况,了解胃贲门癌和胃窦癌的生物学特性及不良预后的原因,指导胃癌术后的治疗。方法选取手术切除的胃贲门癌组织标本64例和胃窦癌组织标本67例,常规病理检查,应用链霉菌亲生物素蛋白-过氧化物酶连接（S-P）免疫组化法检测癌组织中EGFR和VEGF蛋白表达,比较两组患者3年生存率。结果胃贲门癌组EGFR和VEGF蛋白表达率高于胃窦癌组（P〈0．05）。胃贲门癌组患者3年生存率差于胃窦癌组（P〈0．05）。结论胃贲门部癌组织中的EGFR和VEGF基因蛋白过度表达,与胃责门部癌生物学行为差、预后不良存在着密切关系,反映了贲门癌有较高复发和转移危险,提示有加强责门癌手术后辅助治疗的必要性。     

乳腺癌α转化生长因子及表皮生长因子受体免疫组化双重标记研究

目的：研究α转化生长因子（TGFα）及其受体表皮生长因子受体（EGFR）在乳腺癌中的表达特点，以及两者间的相互作用。并通过与已知预后因素的相关分析，研究它们各自在肿瘤发展中的作用。方法：对84例导管浸润型乳腺癌标本进行TGFα－EGFR免疫组织化学双重标记，同时观察两者在非肿瘤及肿瘤组织的表达，并对结果进行单变量和多变量统计学分析。结果：TGFα和EGFR在癌旁组织上皮细胞中均有表达，分别在76．2％和17．8％浸润癌细胞中表达，在16．7％浸润癌细胞中同时表达。χ^2分析显示TGFα在浸润癌细胞中的表达只与ER阴性相关联，而EGFR的表达则与大体积肿瘤、炎性乳癌、腋窝淋巴结受累、不良肿瘤组织学分级（SBRⅢ级）以及雌孕激素受体阴性相关联。多变量统计分析显示，浸润癌细胞中TGFα的表达与炎性乳癌相关联（P＝0．048），而EGFR的表达则与雌激素受体阴性相关联（P＝0．002）。结论：TGFα和EGFR在乳腺癌组织中的表达与在非肿瘤组织中明显不同，并与乳腺癌不良愈后因素相关联，提示他们在乳腺癌的发展中起着重要作用。     

脑膜瘤患者手术前后血清表皮生长因子受体的测定

目的探讨脑膜瘤患者手术前后外周血表皮生长因子受体(EGFR)表达含量的临床意义。方法采用ELISA分析53例脑膜瘤患者(42例肿瘤完全切除和11例肿瘤次全切除)手术前后的血清EGFR含量。28例正常献血者为对照组。结果53例脑膜瘤患者手术前血清EGFR含量(352.93±66.18)fmol/ml明显高于对照组(159.11±40.50)fmol/ml(P<0.0001);手术后(220.74±70.63)fmol/ml明显低于术前组(P<0.001)。其中42例肿瘤完全切除患者中38例的EGFR(191.20±32.13)fmol/ml和4例伴有瘤周水肿患者的EGFR(248.75±10.31)fmol/ml明显低于术前组(P<0.001);11例肿瘤次全切除患者的EGFR(322.14±89.53)fmol/ml与术前组比较无显著性差异(P>0.5)。结论92.16%脑膜瘤患者随着肿瘤切除程度的增高而血清EGFR含量越发降低。提示人脑膜瘤细胞可能自主产生EGFR,血清EGFR测定对脑膜瘤患者手术后追踪可能具有临床意义。     

表皮生长因子受体酪氨酸激酶抑制剂厄洛替尼联合山奈酚诱导卵巢癌细胞凋亡的协同机制

目的: 探讨厄洛替尼和山奈酚对表皮生长因子受体酪氨酸激酶(EGFR-TPK)的抑制作用,并阐明二者对卵巢癌细胞生长的协同抑制作用机制。 方法: 培养人卵巢癌SKOV-3细胞,将细胞分为空白组、山奈酚组和厄洛替尼组,将不同浓度山奈酚与厄洛替尼加入到EGFR-TPK和人卵巢癌SKOV-3细胞中, ELISA法检测EGFR-TPK的活性,采用Transwell小室法检测各组SKOV-3细胞侵袭转移能力,采用酶标仪检测各组SKOV-3细胞凋亡蛋白caspase-3活性,MTT法检测各组SKOV-3细胞的生长抑制率及山奈酚联合厄洛替尼对SKOV-3细胞的生长抑制作用。 结果: 山奈酚和厄洛替尼对EGFR-TPK的半数抑制浓度(IC₅₀)分别为(2.33±0.32)g·L^-1和(1.75±0.18)g·L^-1,二者比较差异无统计学意义(P>0.05)。与空白组比较,山奈酚和厄洛替尼组穿膜细胞数减少(P<0.05或 P<0.01),SKOV-3细胞中凋亡蛋白 caspase-3活性明显增加(P<0.05或 P<0.01)。随着山奈酚和厄洛替尼浓度增加,SKOV-3细胞生长抑制率不断增加,与空白组比较差异均有统计学意义(P<0.05或 P<0.01)。 结论: 山奈酚联合厄洛替尼对人卵巢癌SKOV-3细胞具有协同抑制作用,并对SKOV-3细胞转移起到抑制作用。     

甜菜碱对大鼠肝细胞膜表皮生长因子受体及其酪氨酸蛋白激酶的作用

目的：研究甜菜碱对大鼠肝细胞膜表皮生长因子（ｅｐｉｄｅｒｍａｌｇｒｏｗｔｈｆａｃｔｏｒ，ＥＧＦ）受体及其酪氨酸蛋白激酶（ｔｙｒｏｓｉｎｅｐｒｏｔｅｉｎｋｉｎａｓｅ，ＴＰＫ）活性的影响。方法：应用受体的放射配基结合分析法（ｒａｄｉｏｌｉｇａｎｄｂｉｎｄｉｎｇａｓａｙｏｆｒｅｃｅｐｔｏｒｓ，ＲＢＡ），比较实验组和对照组之间１２５ＩＥＧＦ与其受体的结合情况；受体酪氨酸蛋白激酶活性测定法，以大鼠肝细胞膜可溶性蛋白为酪氨酸蛋白激酶来源，比较实验组和阴性组之间受体蛋白自身磷酸化作用的差异。结果：２６ｎｍｏｌ·Ｌ－１～５．２ｍｍｏｌ·Ｌ－１的甜菜碱均能抑制正常大鼠肝细胞膜ＥＧＦ受体与其配基的结合，这种抑制作用为非竞争性抑制；１０与１００μｍｏｌ·Ｌ－１的甜菜碱可激活酪氨酸蛋白激酶活性，而１０ｍｍｏｌ·Ｌ－１的甜菜碱则抑制酪氨酸蛋白激酶活性。结论：甜菜碱可以抑制ＥＧＦ受体与其配基的结合并影响ＥＧＦ受体的酪氨酸蛋白激酶活性。     

HB-EGF及其受体在不孕症患者子宫内膜中的表达

目的探讨不明原因性不孕症患者子宫内膜中HB-EGF及其受体的表达。方法选择不明原因性不孕症患者30例,正常生育妇女20例,采用免疫组织化学法分析子宫内膜HB-EGF及其受体的表达。结果HB-EGF及其受体EGFR表达在子宫内膜上皮细胞和间质细胞的细胞膜和胞浆中,不明原因性不孕症患者子宫内膜中HB-EGF和EGFR的表达显著低于正常生育妇女组(P<0.05)。HB-EGF和EGFR成正相关(r=0.57,P<0.05)。结论HB-EGF和EGFR的下降可能与不孕症的发生有关。     

表皮生长因子受体在胸腺肿瘤中的表达及其临床意义

目的　探讨表皮生长因子受体 (EGFR)在胸腺瘤发生发展中的作用及临床意义。方法　应用免疫组化S P法检测 2 9例胸腺瘤 ,1 1例正常胸腺组织中的表皮生长因子受体 (EGFR)表达。结果　胸腺瘤EGFR阳性表达率为 75 .9% (2 2 /2 9) ,非常显著高于正常胸腺组织 1 8.2 % (2 /1 1 ) (P <0 .0 1 )。恶性胸腺瘤的阳性表达率 88.9% (1 6 /1 8)非常显著高于良性胸腺瘤 5 4.5 % (6 /1 1 ) (P <0 .0 1 )。胸腺瘤Masaoka分期Ⅲ、Ⅳ期的阳性表达率非常显著高于I期 (P <0 .0 1 )。良性胸腺瘤中无强阳性表达 ,5例强阳性表达的恶性胸腺瘤中 ,术后随访 3例发生局部复发或转移。但EGFR的表达与是否合并重症肌无力 (MG) ,组织学类型无关。结论　提示EGFR的表达与胸腺瘤的发生发展有一定关系 ,EGFR过度表达者复发和转移的危险性较高 ,应加强放疗化疗及术后随访     

中国人脑星形胶质细胞瘤中表皮生长因子受体的表达

目的：研究中国人脑星形胶质细胞瘤中表皮生长因子受体（EGFR）的表达，并探讨其临床意义。方法：应用免疫组化方法（Evision-HRP法）检测人脑星形胶质细胞瘤标本（含配对瘤周组织）以及体外培养的多株人和大鼠胶质瘤细胞系的EGFR表达。结果：人脑星形胶质瘤组织EGFR阳性表达率为70．3％（26／37），明显高于瘤周组织（32．4％，12／37），两者差别非常显著（P＜0．01），病理分级为Ⅲ-Ⅳ级肿瘤标本EGFR阳性表达率为21／25，显著高于I－Ⅱ级者（5／12，P＜0．01）。体外实验显示人脑胶质瘤细胞株U251MG、U87MG以及大鼠脑胶质瘤细胞株C6和EGFR平均表达水平分别为“ ”、“－～＋”、“＋”。结论：中国人脑星形胶质瘤存在EGFR的过度表达，提示EGFR可能是恶性脑胶质瘤细胞的重要标志物。     

人脑胶质瘤中EGFR表达及微血管密度

目的：探讨表皮生长因子受体（EGFR）表达和血管生成在人脑胶质瘤发生发展中的作用以及EGFR表达与血管生成的关系。方法：采用免疫组化SABC和ABC方法分别检测63例人脑胶质瘤中EGFR和Ⅷ因子盯关抗原（FⅧRAg）的表达，计算微血管密度（MVD）。结果：高恶性度（Ⅲ-Ⅳ级）胶质瘤EGFR阳性率为83％，低恶性度（I－Ⅱ级）胶质瘤为58％，二者差异显著（P＜0．05）。EGFR表达随胶质瘤恶性程度增高而增强（P＜0．01）。高恶性度胶质瘤MVD高于低恶性度胶质瘤（P＜0．05）。胶质瘤MVD与EGFR表达呈正相关（γ＝0．899，P＜0．05）。结论：EGFR表达与血管生成是脑胶质瘤发生发展过程中的重要事件，EGFR具有促血管生成作用。     

吴茱萸次碱通过调控表皮生长因子受体活化抑制高血压心肌肥大

探讨抑制表皮生长因子受体(EGFR)活化是否调控中药单体药吴茱萸次碱的抗高血压心肌肥大效应及其机理。以腹主动脉缩窄(AAC)介导的高血压大鼠为研究对象,观察吴茱萸次碱对高血压心肌肥大、心肌炎症反应以及左心室中EGFR和细胞外调节蛋白激酶1/2(ERK1/2)活性的影响。结果显示,吴茱萸次碱能显著抑制AAC介导的高血压心肌肥大、心肌炎症反应以及EGFR、ERK1/2活化。并且,选择性EGFR抑制剂AG1478能改善AAC介导的高血压心肌肥大和心肌炎症反应,抑制ERK1/2活化。结果提示,吴茱萸次碱通过抑制EGFR活化改善AAC介导的高血压大鼠心肌肥大,其机制与其抑制ERK1/2活化和心肌炎症反应有关。     

雌激素对乳腺癌细胞的生长及p185蛋白和表皮生长因子受体表达的影响

为了研究乳腺癌的发展过程中雌二醇（Ｅ＿２）的作用机制及参与因素，作者使用流式细胞仪观察了人乳腺癌细胞株ＳＫ－ＢＲ－３在Ｅ＿２作用下的生长特征及ｐ１８５蛋白和表皮生长因子（ＥＧＦ）受体的表达．结果表明，乳腺癌细胞生长加快，ＤＮＡ合成增加，Ｓ期百分率升高（Ｅ＿２组２６．７±２．５，对照组２１．２±２．１，Ｐ＜０．０５）．在Ｅ＿２的作用下，乳腺癌细胞的ｐ１８５蛋白表达降低（Ｅ＿２３５±５．６，对照组６１±１３．１，Ｐ＜０．０５）而ＥＧＦ受体表达升高（Ｅ＿２３９±６．９，对照组２１±５．４，Ｐ＜０．０５），提示ＥＧＦ在乳腺癌的早期发展中可能发挥更主要的作用．     

Correlation of epidermal growth factor receptor overexpression with increased epidermal growth factor receptor gene copy number in esophageal squamous cell carcinomas

Background  Esophageal squamous cell carcinoma (ESCC) is one of the most frequent malignancies in China and epidermal growth factor receptor (EGFR) is widely distributed in human epithelial cell membrane. The aim of this study was to investigate the protein overexpression and gene copy number of EGFR in ESCC, and help to identify patients who may benefit from EGFR targeted therapies.  

Methods  Immunohistochemistry (IHC) was performed to analyze the expression of EGFR in 105 cases of ESCC, 16 cases of squamous epithelial atypical hyperplasia, and 11 cases of normal esophageal tissue. Fluorescence in situ hybridization (FISH) was performed to analyze the gene copy number in 80 cases of ESCC, eight cases of squamous epithelial atypical hyperplasia, and eight samples of normal esophageal tissue.

Results  The IHC-positive rates of EGFR in 105 cases of ESCC, 16 cases of squamous epithelial atypical hyperplasia, and 11 normal esophageal tissues were 97% (102/105), 44% (7/16), and 18% (2/11) respectively. The difference in the expression of EGFR among different esophageal tissue groups had statistically significance (P <0.05). Among the 105 cases of ESCC, overexpression of EGFR was found in 90 cases (86%), of which 55 cases scored 3+ for EGFR staining and 35 cases scored 2+. In ESCC, the expression of EGFR was significantly correlated with depth of invasion and TNM stage (P <0.05), but not with other parameters. The FISH-positive rates of EGFR in 80 cases of ESCC, the eight cases of squamous epithelial atypical hyperplasia, and eight samples of normal esophageal tissue were 31.3% (25/80), 0 (0/8) and 0 (0/8) respectively. In ESCC, EGFR gene amplification was found in 17 (21%) cases, high polysomy in 8 (10%) cases, disomy in 34 cases, low trisomy in 17 cases, and high trisomy in four cases. EGFR FISH-positive was significantly correlated with depth of invasion and lymph node metastasis (P <0.05). EGFR FISH-positive was significantly associated with overexpression of EGFR.

Conclusion  Protein overexpression and/or increased gene copy number of EGFR is common in ESCC, and EGFR targeted therapy may be appropriate for ESCC patients.