食管鳞癌组织β-catenin表达与淋巴管生成的关系

目的研究食管鳞癌组织中β-catenin表达与淋巴管生成的关系。方法应用免疫组织化学SP法检测68例食管鳞癌标本及20例癌旁正常黏膜组织中β-catenin蛋白的表达状态,特异性淋巴管内皮标记物Podoplanin检测癌及正常黏膜组织的淋巴管密度(LVD),分析β-catenin异位表达和LVD与各临床病理指标的关系,并探讨二者之间的相关性。结果 1正常食管黏膜β-catenin均表达于细胞膜,而食管癌鳞组织中β-catenin主要呈细胞质/细胞核的异位表达,表达率为82.4%(56/68),且β-catenin的异位表达与淋巴结转移(χ2=7.275,P=0.007)和外膜浸润(χ2=6.236,P=0.013)明显相关。2食管鳞癌组织中的LVD显著高于正常组织(t=2.946,P=0.002),淋巴结转移组的LVD也明显高于无淋巴结转移组(t=7.521,P=0.001)。3β-catenin异位表达的食管鳞癌组织与β-catenin仅表达于细胞膜的LVD比较差异显著(t=2.926,P=0.008)。结论β-catenin异位表达可能是诱导食管癌淋巴管生成的重要原因。     

食管鳞癌患者podoplanin表达及微淋巴管密度与淋巴转移的关系

对78例食管鳞癌术后组织标本进行免疫组化染色,观察podoplanin在食管鳞癌组织的表达情况,计数微淋巴管密度(LMVD),并分析LMVD与临床病理参数的关系.结果 podoplanin在淋巴内皮细胞上表达,在食管鳞癌细胞上不表达;不同侵润深度、有无淋巴结转移、不同临床分期食管鳞癌患者LVMD比较差异有统计学意义(P均<0.05).认为用podoplanin免疫组化法评估食管癌患者的淋巴管生成来预测淋巴结转移有一定的临床价值.     

癌相关成纤维细胞与食管鳞状细胞癌淋巴转移及淋巴管生成的相关性研究

目的探讨食管鳞状细胞癌中癌相关成纤维细胞浸润与淋巴转移及淋巴管生成的关系。方法本研究中收集53例手术切除并病理确诊的食管鳞状细胞癌新鲜组织,25例距癌灶>5 cm的正常食管黏膜新鲜组织,并统计患者性别、年龄、病理级别、浸润深度、淋巴结是否转移等临床病理资料,应用免疫组织化学染色法检测癌相关成纤维细胞标记蛋白α-SMA以及淋巴管内皮细胞标记蛋白D2-40。采用SPSS 21.0统计学软件对数据进行分析。结果食管鳞状细胞癌组织中癌相关成纤维细胞数量与微淋巴管密度均高于正常食管黏膜组织(P<0.05)。食管鳞状细胞癌组织中癌相关成纤维细胞数量与临床分期、浸润深度、肿瘤淋巴结转移密切相关(P<0.05),与性别、年龄无关。食管鳞状细胞癌组织中癌相关成纤维细胞数量与微淋巴管密度呈正相关(P<0.05)。结论癌相关成纤维细胞可能通过促进淋巴管生成参与食管鳞状细胞癌的浸润和转移,这可能为食管鳞状细胞癌的早期预防和靶向治疗提供新方向。     

食管鳞癌患者血清中VEGF的表达变化及意义

目的观察食管鳞癌患者血清血管内皮生长因子（VEGF）的表达变化,并探讨其意义。方法采用ELISA法检测46例食管鳞癌患者和10名健康体检者外周静脉血血清中的VEGF。结果食管癌患者血清VEGF水平为（502.176±65.218）pg/ml,对照组为（311.648±40.984）pg/ml,两组相比,P〈0.01;根据肿瘤国际TNM分期标准：食管癌组Ⅰ期＋Ⅱ期者血清VEGF水平为（446.890±50.602）pg/ml,Ⅲ期者为（580.012±56.996）pg/ml,两组相比,P〈0.01;浸润深度T1＋T2者血清VEGF水平为（434.725±49.703）pg/ml,T3者为（503.504±68.500）pg/ml、T4者为（595.441±48.192）pg/ml,三者相比,P均〈0.01;有淋巴结转移者血清VEGF水平为（576.011±61.798）pg/ml,高于无淋巴结转移者的（464.340±68.639）pg/ml,P〈0.01。结论食管鳞癌患者血清VEGF表达升高,与肿瘤的发生、浸润深度、淋巴结转移情况及TNM分期相关。VEGF是食管鳞癌发生发展预后判断的一个有价值的依据。     

食管鳞癌组织中IGF-1R、VEGF-C的表达变化及意义

目的观察食管鳞癌组织中的胰岛素样生长因子-1R（IGF．1R）、血管内皮生长因子C（VEGF—C）的表达变化,并探讨其意义。方法分别采用免疫组化法、免疫印迹法检测食管鳞癌和癌旁正常食管组织中的IGF-1R、VEGF—C。结果食管鳞癌组织中IGF-1R、VEGF—C阳性率分别为81．05％、67．37％,癌旁组织中分别为20％、5％,P均〈0．01;食管鳞癌组织中IGF—IR、VEGF．C蛋白条带灰度比值分别为0．58土0．03、0．43±0．05,癌旁组织中分别为0．43±0．02、0．31±0．04,P均〈0．05。IGF—IR、VEGF—C表达与食管鳞癌淋巴结转移、浸润深度有关（P均〈0．01）,二者表达呈正相关（r=0．29,P〈0．05）。结论食管鳞癌组织中IGF—IR、VEGF—C高表达,在食管鳞癌的发生发展及转移中有重要作用。     

胰腺癌组织中COX-2、VEGF-C表达和淋巴管密度

目的 检测胰腺癌及癌旁组织中COX-2、VEGF-C的表达与淋巴管密度(LVD),探讨它们之间的关系.方法 应用组织芯片技术和免疫组化方法检测40例胰腺癌及相应癌旁组织和12例远处正常胰腺组织中COX-2、VEGF-C的表达及LVD,分析它们之间的关系,以及与临床病理指标的关系.结果 胰腺癌组织COX-2、VEGF-C表达阳性率分别为70.0%(28/40)和67.5%(27/40),显著高于癌旁组织的42.5%(17/40)和35.O%(14/40,P＜0.01),也显著高于正常胰腺的8.3%(1/12)和25.0%(3/12).癌、癌旁及正常胰腺的LVD分别为4.75±2.77、15.20±4.70和1.67±1.15,以癌旁组织最高(P＜0.01).癌组织COX-2表达与肿瘤分化程度、淋巴结转移相关;VEGF-C的表达与淋巴结转移相关.癌旁组织LVD与肿瘤分化程度、淋巴结转移有关,并与癌组织COX-2、VEGF-C表达存在一定相关性.结论 胰腺癌新生淋巴管主要存在于癌旁,淋巴管的形成可能有COX-2及VEGF-C的参与.     

食管鳞癌组织中NF-κB p65、VEGF的表达及其与血管密度测定的意义

采用免疫组化S-P法检测61例食管鳞癌患者组织中核转录因子-κB（NF-κB）p65和血管内皮生长因子（VEGF）的表达及CD105标记的肿瘤内徽血管密度（MVD）。结果NF-κB p65表达与食管鳞癌的组织学分级、浸润深度和淋巴结转移均呈正相关（P均〈0．01）,VEGF蛋白表达及MVD与食管鳞癌组织学分级和浸润深度均无关,但与淋巴结转移呈正相关（P〈0．05）;NF-κB p65与VEGF表达呈正相关（P〈0．01）;二者均与MVD呈正相关（P均〈0．05）。提示NF-κB p65参与食管鳞癌的发生、发展,其机制可能与VEGF的表达和肿瘤血管生成有关。     

瘤内淋巴管生成与喉鳞癌淋巴转移的关系

选择我喉鳞状细胞癌（LSCC）标本60例，行双重免疫组化染色法计数喉鳞癌瘤内淋巴管。发现喉鳞癌瘤内有新生淋巴管，瘤内淋巴管密度（LVD）与N分期及临床分型存在相关关系。认为瘤内LVD的增高与肿瘤淋巴转移有关。     

食管鳞癌组织中VEGFR-2基因扩增情况观察及与患者预后关系分析

目的 观察食管鳞癌组织中血管内皮生长因子受体-2(VEGFR-2)基因扩增情况,并分析VEGFR-2基因扩增与食管鳞癌患者预后的关系。方法 食管鳞癌患者120例,术中留取食管癌组织,采用荧光原位杂交（FISH）法观察食管鳞癌组织中VEGFR-2基因扩增情况,并分析VEGFR-2基因扩增与食管鳞癌患者临床病理参数的关系。根据有无VEGFR-2基因扩增,将120例食管鳞癌患者分为阳性组（VEGFR-2基因扩增阳性）和阴性组（VEGFR-2基因扩增阴性）,采用Kaplan-Meier生存分析法及多因素COX回归模型分析VEGFR-2基因扩增与食管鳞癌患者预后的关系。结果 120例食管鳞癌患者中,49例患者存在VEGFR-2基因扩增,VEGFR-2基因扩增率为40.8%。VEGFR-2基因扩增与食管鳞癌患者肿瘤分化程度、有无淋巴结转移、有无脉管浸润有关（P均<0.05）。阴性组的食管鳞癌患者生存时间为16(11.15～20.84)个月,阳性组为13(8.27～17.72)个月,两组相比,P<0.05。多因素COX回归分析结果显示,VEGFR-2基因扩增是食管鳞癌患者不良预后的独立危...     

促淋巴管生长因子与NSCLC淋巴管新生及转移的研究进展

淋巴结转移是非小细胞肺癌(NSCLC)及其他恶性肿瘤重要的不良预后因素之一.研究表明,NSCLC及癌旁组织中存在大量淋巴管新生,并且在促进肿瘤细胞淋巴结转移过程中发挥重要作用.目前研究发现NSCLC淋巴管新生及转移受多种促淋巴管生长相关因子的调节,现对其研究进展作一综述.     

Expression of thymidylate synthase and glutathione-s- transferase π in patients with esophageal squamous cell carcinoma

AIM： To investigate the expression of thymidylate synthase （TS） and glutathione-s-transferase π （GST-π） in esophageal squamous cell carcinoma and their association with the clinicopathologic characteristics. METHODS： Immunohistochemical methods were used to detect the expression of TS and GST-π in surgically resected formalin-fixed, paraffin-embedded esophageal squamous cell carcinoma （ESCC） tissue sections from 102 patients （median age, 58 years） and in 28 normal esophageal mucosa （NEM） samples. The relationship between TS and GST-π expression and clinicopathologic factors was examined. RESULTS： The expression of TS and GST-π was not statistically significantly associated with age of the patients, tumor size, lymph node metastasis, depth of invasion or tumor stage. TS staining was positive in 17.86% of normal esophageal mucosa and in 42.16% of ESCC samples （P 〈 0.05）. The expression level of TS was not only significantly lower in well-differentiated （21.88%） than in poorly-differentiated carcinomas （51.43%, P 〈 0.05）, but was also significantly higher in samples from male patients （46.51%） than from female patients （18.75%, P 〈 0.05）. GST-π was positively stained in 78.57% of normal esophageal mucosa and in 53.92% of ESCC samples （P 〈 0.05）. The expression level of GST-π was also significantly higher in welldifferentiated carcinomas （65.63%） than in poorly- differentiated carcinomas （35.00%, P 〈 0.05）. CONCLUSION： The expression of TS and of GST-π may be used as molecular markers for the characterization of ESCC. Poorly-differentiated cells showed increased expression of T5 and reduced expression of GST-π.     

肌动蛋白凝胶蛋白在食管鳞癌中的表达及其与临床病理因素的关系

目的探讨肌动蛋白凝胶蛋白(Transgelin)在食管鳞癌组织中的表达及其与临床病理因素间的关系。方法采用免疫组化法检测Transgelin在食管鳞癌组织、癌旁不典型增生组织及正常食管黏膜组织中的表达,并分析Transgelin的表达与患者临床病理因素特征的关系及其对预后的影响。结果Transgelin在食管鳞癌中的阳性率明显高于癌旁不典型增生组和正常食管黏膜组织,其差异有统计学意义(P<0.05)。Transgelin在食管癌中的表达与患者的的TNM分期(P<0.05)、淋巴结转移(P<0.05)、远处转移(P<0.05)有关;与患者的性别、年龄、肿瘤直径无关(P>0.05)。在随访的210例患者中,Transgelin的生存曲线显示,高表达组Transgelin的5年生存率明显低于低表达组(P<0.05)。单因素生存分析显示,Transgelin的表达水平、TNM分期、淋巴结转移、远处转移与食管鳞癌患者术后生存时间相关。同时,多因素Cox比例风险回归模型分析显示,Transgelin的表达水平、TNM分期、淋巴结转移和远处转移为食管鳞癌患者预后的独立危险因素。结论Transgelin在食管鳞癌组织中呈高表达,其表达与食管鳞癌的发生发展和侵袭转移相关,Transgelin对于术后食管鳞癌患者的预后评估具有参考价值。     

Expression of midkine and its clinical significance in esophageal squamous cell carcinoma

AIM: TO investigate the expression of midkine in esophageal squamous cell carcinoma (ESCC) and analyze its relationship with clinicopathological features. METHODS: RT-PCR and immunocytochemical staining were used to detect the expression of midkine mRNA and protein in EC109 cells, respectively. Then the expression of midkine in 66 cases of ESCC samples were detected by immunohistochemistry using monoclonal antibodies against human midkine. RESULTS: Midkine was expressed in EC109 cell by RT-PCR and immunocytochemistry. The immunoreactivity was detected in 56.1% (37/66) of the ESCC samples. The expression of midkine was found in cytoplasm of tumor cells. Notably, the intensity of midkine was stronger at the area abundant in vessels and the invading border of the tumors. Midkine was more intensely expressed in well differentiated tumors (76.9%) than in moderately and poorly differentiated tumors (43.1% and 41.2%, respectively) (P<0.05). There was no statistically significant correlation between midkine expression and gender, age, clinical stage, lymph node metastasis or survival in ESCC. CONCLUSION: Midkine is overexpressed in ESCC. It may play a role in tumor angiogenesis and invasion. The expression of midkine is correlated with tumor cell differentiation in ESCC. The more poorly tumor cells differentiate, the weaker midkine expresses.     

膜联蛋白A2在食管鳞状细胞癌中的表达及其与浸润转移的关系

目的 探讨膜联蛋白A2(Annexin A2)在人食管鳞状细胞癌(ESCC)中的表达变化与浸润转移的关系.方法 收集新疆医科大学第一附属医院2000年至2008年间,手术切除并经病理证实的ESCC组织作为实验组、对应癌旁5cm以上的组织作为对照组;随机选取了ESCC与癌旁配对的22对新鲜组织和175对石蜡包埋组织作为研究对象.应用实时荧光定量PCR(real-time quantitative PCR,qRT-PCR)、蛋白免疫印迹和免疫组织化学的方法,从mRNA和蛋白两个方面检测Annexin A2的表达,并分析其与临床病理参数的关系.结果 在22对新鲜ESCC与癌旁组织中,Annexin A2在癌旁组织中的mRNA表达量(0.06±0.06)显著高于癌组织(0.02±0.02,P<0.05);Annexin A2在癌旁组织中的蛋白表达量(0.95±0.42)高于癌组织(0.81±0.36,P<0.05).在175对ESCC与癌旁组织石蜡标本中,Annexin A2蛋白的阳性表达率为82.3%(144/175),低于配对的癌旁组织中的阳性表达率[92.0%(161/175),P<0.05].此外,Annexin A2的表达与ESCC患者的淋巴结转移及分化程度相关(P<0.05),而与ESCC患者的大体类型关系不明显(P＞0.05).结论 Annexin A2在ESCC中的低表达可能对ESCC的发生发展及浸润转移起着一定的作用.     

Clinicopathologic factors predicting lymph node metastasis in superficial esophageal squamous cell carcinoma

Abstract

Objective. Surgical resection is the treatment of choice for superficial esophageal squamous cell carcinoma (SESCC), but it is associated with high mortality and morbidity rates. Recently, endoscopic resection for SESCC has been indicated for patients with a low risk of lymph node metastasis (LNM). Therefore, to successfully treat SESCC with endoscopic resection, it is very important to identify patients with a low risk for LNM. The objective of this study was to investigate clinicopathologic factors that predict LNM in patients who underwent esophagectomy for SESCC. Methods. The study included 104 patients with SESCC from three university hospitals in Pusan, Korea. Clinicopathologic factors were evaluated to identify independent factors predicting LNM by univariate and multivariate analyses. Results. In univariate analysis, the depth of tumor invasion and lymphovascular invasion had significant influences on LNM (p = 0.001 and p < 0.001, respectively). Gross type, tumor size, and tumor differentiation were not predictive for LNM. In multivariate analysis, the depth of tumor invasion and lymphovascular invasion were signi?cantly associated with LNM in patients with SESCC (OR 9.04, p = 0.049; OR 11.61, p = 0.002, respectively). Conclusions. The depth of tumor invasion and lymphovascular invasion were independent predictors of LNM in patients with SESCC. Therefore, endoscopic resection could be performed in patients with SESCC that is limited to the mucosa, without lymphovascular invasion.     

鸟氨酸脱羧酶与食管鳞癌血管生成相关性的研究

目的 研究ODc mRNA和MVD在食管鳞癌中的表达及相关关系,探讨ODC在食管鳞癌血管生成中的可能作用及其与肿瘤浸润和转移的关系。方法 研究对象为41例经手术和病理证实的食管鳞癌患者,用RT-PCR方法测定癌组织和相应癌旁正常组织的ODC mRNA表达,以β-actin做内参照求得各自T/N值;用免疫组化方法测定癌组织和癌旁正常组织的MVD的T/N值。结果 在41例中,39例ODc mRNA的T/N值>1.0,占95.1％;40例MVD的T/N值>1.0,占97.6％。ODC mRNA和MVD与食管鳞癌的肿瘤大小、浸润深度和淋巴结转移有关,ODC mRNA与肿瘤分化程度有关。ODC mRNA的T/N值与MVD的T/N值正相关。结论 ODC与食管鳞癌血管生成和肿瘤浸润转移密切相关。ODC可能是通过影响血管生成而促进食管鳞癌的浸润和转移。     

Overexpression of Ets-like protein 1 in human esophageal squamous cell carcinoma

INTRODUCTION Esophageal cancer ranks among the 10 most frequent cancers in the world, with a predominant distribution in developing countries. It is one of the most common malignant tumors in China[1,2]. Our previous study showed that genetic susceptibili…     

TWEAK及其受体Fn14蛋白在食管鳞癌中的表达及临床病理意义

目的:探讨肿瘤坏死因子样凋亡微弱诱导剂(TNF-like weak inducer of apoptosis,TWEAK)及其受体早期反应蛋白14(fibroblast growth factor-inducible 14,Fn14)表达与食管鳞状细胞癌发生、发展及浸润、转移的关系.方法:应用免疫组化法分别检测手术切除的45例食管鳞癌组织、22例癌旁不典型增生组织及22例正常食管黏膜组织中TWEAK及Fn14蛋白表达,并且对二者在食管鳞状细胞癌组织中的表达情况进行相关性分析.结果:食管鳞癌组织中TWEAK蛋白表达与癌的浸润深度、淋巴结转移及TNM分期均密切相关(χ2分别为6.455,11.645及4.185,P均<0.05);在食管鳞癌癌变过程中TWEAK蛋白表达在正常黏膜组织、癌旁不典型增生组织及癌组织中的表达率依次增高,分别为27.3%(6/22)、40.9%(9/22)、64.4%(29/45),组间比较差异具有统计学意义(χ2=9.018,P<0.05);Fn14蛋白表达也与癌的组织学分级、浸润深度、淋巴结转移及TNM分期均密切相关(χ2分别为10.873、12.513、9.244及13.137;均P...     

Expression of OCT4 in human esophageal squamous cell carcinoma is significantly associated with poorer prognosis

AIM: To explore the expression pattern of OCT4 in human esophageal squamous cell carcinoma and its significance in diagnosis and prognosis.METHODS: Using real-time polymerase chain reaction (PCR), Western blotting, immunocytochemistry and immunohistochemistry, the expression of OCT4 in three esophageal squamous cancer cell lines, KYSE70, KYSE140 and KYSE450, was characterized. OCT4 expression was investigated in a series of 153 esophageal squamous cell carcinoma samples using immunohistochemistry and explored its association with clinicopathological features.RESULTS: Immunohistochemically, OCT4 positive immunostaining was observed in cancer cell nuclei. OCT4 was variably expressed in three esophageal squamous cancer cell lines. Among 153 specimens, 105 (68.7%) were negative or weakly positive for OCT4 staining; 21 (13.7%) were moderately positive and 27 (17.6%) were strongly positive. Higher expression level of OCT4 was significantly associated with higher histological grade (P < 0.001) and poor clinic outcome (P < 0.001).CONCLUSION: The expression of OCT4 enables the tumor to have a higher degree of stemness, which in turn results in a poorer clinical outcome for patients with esophageal squamous cell carcinoma.