Expression of the EphA2 Gene in Esophageal Carcinoma Tissues

OBJECTIVE To investigate the relationship of the EphA2 gene with the occurrence, invasion and metastasis of esophageal carcinoma. METHODS The expression of EphA2 mRNA was detected by RT-PCR and the EphA2 protein was estimated by immunohistochemistry (SP method) in both esophageal cancerous tissues and normal epithelial tissues. RESULTS The expression of EphA2 mRNA showed no difference between esophageal cancerous tissues and normal epithelium, and there appeared to be no correlation with differentiation of the cancerous tissues, the depth of infiltration or lymph node metastasis (P>0.05). However, the expression of the EphA2 protein was significantly higher in cancerous tissues compared to normal epithelial tissues (P<0.05). The expression of the EphA2 protein in a deeper invasive group and in a group with lymph node metastasis was significantly higher compared to a superficially invasive group and a group without lymph node metastasis (P<0.05). Its expression did not appear to be correlated with differentiation of cancerous tissues (P>0.05). CONCLUSION The occurrence of esophagus carcinoma and the formation of invasion and metastasis may be related to overexpression of the EphA2 protein but not to the level of mRNA, a finding which may due to up-regulation at the translation level or by increased protein stability.

Relationship between HER-2 overexpression and brain metastasis in esophageal cancer patients

AIM:To study if HER-2 overexpression by locally advanced esophageal cancers increase the chance of brain metastasis following esophagectomy.METHODS:We retrospectively reviewed the medical records of esophageal cancer patients who underwent esophagectomy at University of Iowa Hospitals and Clinics between 2000 and 2010.Data analyzed consisted of demographic and clinical variables.The brain metastasis tissue was assayed for HER-2 overexpression utilizing the FDA approved DAKO Hercept Test.RESULTS:One hundred and forty two patients were reviewed.Median age was 64 years(36-86 years).Eighty eight patients(62%) received neoadjuvant chemoradiotherapy.Pathological complete and partial responses were achieved in 17(19%) and 71(81%) patients.Cancer relapsed in 43/142(30%) patients.The brain was the first site of relapse in 9/43 patients(21%,95% CI:10%-36%).HER-2 immunohistochemistry testing of the brain metastasis tissue showed that 5/9(56%) cases overexpressed HER-2(3+ staining).CONCLUSION:HER-2 overexpression might be associated with increased risk of brain metastasis in esophageal cancer patients following esophagectomy.Further studies will be required to validate this observation.

EphA2基因在食管癌组织中的表达及其意义

目的:探讨EphA2基因(包括mRNA和蛋白水平)的表达与食管癌发生及浸润转移的关系。方法:采用RT-PCR及免疫组化方法,检测食管癌组织及其正常粘膜中EphA2mRNA及蛋白的表达。结果:EphA2mRNA的表达在食管癌组织和其正常粘膜中未见显著性差异(P>0.05),且与肿瘤的分化程度、浸润深度及淋巴结转移无关(P>0.05)。EphA2蛋白在食管癌组织中的表达明显高于其正常粘膜(P<0.05),在深层浸润者的表达明显高于浅层浸润者(P<0.05),在有淋巴结转移者中的表达明显高于无淋巴结转移者(P<0.05),但与肿瘤的分化程度无关(P>0.05)。结论:EphA2蛋白的高表达可能与食管癌的癌变及侵袭转移的发生有关,但与EphA2mRNA的表达无关,推测这可能是由于翻译水平上调或蛋白质稳定性增高所致。

食管胃结合部腺癌术后患者预后的相关因素研究

目的研究食管胃结合部腺癌术后患者预后的相关因素。方法入选食管胃结合部腺癌患者173例,从手术结束开始随访5年为研究终点,统计患者的1、3、5年生存率和中位生存时间。分析年龄、性别、淋巴结转移、是否化疗、HER-2表达与否等因素与该病的相关性。结果经过5年随访,食管胃结合部腺癌患者在1、3、5年的生存率分别为87.9%、48.6%、44.5%,中位生存期为38.0月。分别统计和分析患者的各项因素,其中性别(P=0.000)、年龄(P=0.012)、TNM分期(P=0.000)、淋巴结转移(P=0.000)、化疗(P=0.000)、HER-2表达(P=0.000)等因素的差异均具有统计学意义。结论食管胃结合部腺癌患者术后生存期与性别、年龄、TNM分期、淋巴结转移、是否化疗、HER-2表达均有不同程度的关联,值得进一步研究。

组织因子途径抑制物-2和γ-神经突触核蛋白在食管癌中的表达及其与肿瘤细胞浸润、转移和凋亡之间的关系

目的:探讨组织因子途径抑制物-2(tissue factor pathway inhibitor-2,TFPI-2)和γ-神经突触核蛋白(synuclein gamma,SNCG)在食管癌组织中的表达及其与肿瘤浸润、转移和细胞凋亡之间的关系。方法:应用免疫组织化学法检测82例食管癌组织及20例相应癌旁不典型增生组织和54例相应癌旁正常食管组织中TFPI-2、SNCG和基质金属蛋白酶-9(matrix metallo-proteinase-9,MMP-9)的表达,应用TUNEL法检测肿瘤细胞的凋亡并计算细胞凋亡指数(apoptosis index,AI)。结果:TFPI-2和SNCG在食管癌组织、癌旁不典型增生组织及正常食管组织中的阳性表达率分别为30.4%、60.0%、87.0%和63.4%、30.0%、3.7%,3组间两两比较差异均有统计学意义(P<0.01)。TFPI-2和SNCG的表达与肿瘤淋巴结转移、浸润深度、TNM分期和分化程度密切相关(P<0.01),但与患者年龄、性别、肿瘤大小、肿瘤部位和肿瘤大体分型无关(P>0.05)。食管癌组织中TFPI-2与MMP-9的表达呈负相关(r=-0.636,P=0.000),而SNCG与MMP-9的表达呈正相关(r=0.393,P=0.000)。TFPI-2和SNCG的表达与AI有关(P<0.05)。结论:TFPI-2可能通过抑制MMP-9的表达诱导细胞凋亡,抑制食管癌细胞的生长和转移,而SNCG可能在此过程中起着相反的作用,TFPI-2和SNCG有望成为有效的肿瘤标志物和肿瘤基因治疗的新靶点。

MTA2在食管鳞癌组织中高表达并与食管癌KYSE510细胞的增殖和迁移有关

目的:探讨转移相关基因2(metastasis-associated gene 2,MTA2)在食管癌组织中的表达以及对食管癌KYSE510细胞增殖和迁移的影响。方法:选取2014年在河北医科大学第四医院进行手术切除的50例食管癌组织及其相应的癌旁组织,应用实时荧光定量PCR检测MTA2和转录因子特异性蛋白1(specifi city protein 1,Sp1)m RNA的表达。将MTA2-si RNA和阴性对照si RNA片段转染至食管癌KYSE510细胞后,应用MTS实验和Transwell实验检测KYSE510细胞的增殖、迁移和侵袭情况,应用蛋白质印迹法检测KYSE510细胞中与上皮-间质转化(epithelialmesenchymal transition,EMT)相关蛋白的表达情况。结果:食管癌组织中MTA2 m RNA的表达水平显著高于相应的癌旁组织(P<0.05),并且与肿瘤的TNM分期(P<0.05)、淋巴结转移和血管浸润有关(P值均<0.01)。食管癌组织中Sp1 m RNA的表达水平显著高于相应的癌旁组织(P<0.05),且MTA2 m RNA的表达水平与Sp1 m RNA的表达水平呈正相关(r=0.407,P=0.028)。MTA2-si RNA转染组细胞的增殖、迁移和侵袭能力显著低于阴性对照组(KYSE510细胞转染阴性对照si RNA片段)和空白对照组(KYSE510细胞未进行任何转染)(P值均<0.05)。MTA2-si RNA转染组细胞中E-cadherin的表达水平上调(P<0.05),而N-cadherin、vimentin和CD24蛋白的表达水平下调(P<0.05、P<0.01和P<0.05)。结论:食管癌中MTA2 m RNA的表达水平上调,可能与转录因子Sp1的表达水平升高有关。MTA2-si RNA可抑制食管癌KYSE510细胞的增殖、迁移和侵袭,这一作用可能与EMT有关。