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。     

食管鳞癌患者血清VEGF、Endostatin水平变化及意义

目的观察食管鳞癌患者血清血管内皮生长因子（VEGF）和内皮抑素（Endostatin）的水平变化,并探讨其意义。方法采用ELISA法检测126例食管鳞癌患者和14例健康对照者血清VEGF及Endostatin。结果食管鳞癌患者血清VEGF为（20.68±3.09）μg/L、Endostatin为（4.96±1.72）μg/L,健康对照者分别为（3.82±6.28）μg/L（、1.60±0.37）μg/L,两组相比,P均〈0.05。食管鳞癌患者血清中VEGF、Endostatin水平与肿瘤分化程度、TNM分期、肿瘤直径、淋巴结转移有关（P均〈0.01）,其血清VEGF与Endostatin的水平呈正相关（r=0.594,P〈0.01）。结论食管鳞癌患者血清VEGF、Endostatin水平升高,可作为食管鳞癌恶性程度及肿瘤负荷的预测指标。     

食管鳞癌组织中hMLH1 mRNA的表达变化及意义

目的观察食管鳞癌组织中错配修复基因hMLH1 mRNA的表达变化,并探讨其临床意义。方法采用RT-PCR法检测60例食管鳞癌组织与癌旁组织中的hMLH1 mRNA。结果食管鳞癌组织中hMLH1 mRNA相对表达量（0.761 7±0.035 7）明显低于癌旁正常组织（1.025 2±0.047 4）,P〈0.05;hMLH1 mRNA的相对表达量与食管鳞癌分化程度、肿瘤浸润深度和淋巴结转移无关（P均〉0.05）,与病理分期有关（P〈0.05）。结论hMLH1 mR-NA表达缺失参与了食管鳞癌的发生或发展。     

宫颈鳞癌组织中VEGF-C、VEGFR-3的表达变化及意义

目的观察血管内皮生长因子C（VEGF-C）及其受体（VEGFR-3））在宫颈上皮内瘤变（CIN）及宫颈鳞癌组织中的表达变化,探讨其与宫颈癌发生发展及浸润转移的关系。方法采用免疫组化SP法检测11例正常宫颈组织、19例CIN及47例宫颈鳞癌组织中的VEGF-C、VEGFR-3。结果VEGF-C与VEGFR-3在正常宫颈组织、CIN及宫颈鳞癌组织中的表达依次增高,三者相比,P〈0．05。在宫颈鳞癌组织中VEGF-C与VEGFR-3的表达有关（P〈0．01）,淋巴结转移组VEGF-C与VEGFR-3的阳性表达率明显高于无转移组（P〈0．05）。结论VEGF-C和VEGFR-3在宫颈鳞癌发生发展及淋巴转移过程中发挥重要作用。     

BAG-1在食管鳞癌组织中的表达及意义

采用免疫组化S-P法检测92份食管鳞癌组织和20份正常食管黏膜中抗凋亡基因BAG-1的表达,并采用TNUEL法检测细胞凋亡指数。结果食管鳞癌组织BAG-1阳性表达率为70．6％（65／92）,明显高于正常食管黏膜组织15％（3／20）,差异有统计学意义BAG-1表达与癌组织分化程度、TNM分期、淋巴结转移密切相关;随BAG-1表达强度的增加,癌细胞凋亡指数逐渐降低。认为BAG-1能抑制癌细胞调亡,其表达与食管鳞癌的发生、发展密切相关,可作为食管鳞癌治疗的新靶点。     

食管鳞状细胞癌组织中VEGF、MMP-9的表达及意义

目的观察食管鳞状细胞癌（鳞癌）组织中血管内皮细胞生长因子（VEGF）和基质金属蛋白酶-9（MMP-9）的表达,并探讨其临床意义。方法采用免疫组化SP法检测60例手术切除的食管鳞癌组织、癌旁组织、切缘正常食管黏膜组织中的VEGF和MMP-9。结果食管鳞癌组织中的VEGF和MMP-9在明显高于癌旁组织和正常食管黏膜（P均〈0.05）。食管鳞癌组织中的VEGF和MMP-9与淋巴转移、浸润深度、TNM分期有关（P均〈0.05）。食管鳞癌组织中的VEGF和MMP-9呈正相关（r=0.421,P〈0.05）。结论食管鳞癌组织中VEGF和MMP-9表达增高。二者与食管鳞癌的发生发展有关。     

非小细胞肺癌组织中IGF-1R、IGFBP-2的表达变化及意义

目的观察非小细胞肺癌（NSCLC）组织中胰岛素样生长因子1受体（IGF-1R）、胰岛素样生长因子结合蛋白2（IGFBP-2）的表达变化,并探讨其意义。方法采用免疫组化SP法检测44例NSCLC组织和30例癌旁组织中的IGF-1R、IGFBP-2。结果 IGF-1R、IGFBF-2在NSCLC组织中的阳性表达率分别为72.7%、77.3%,癌旁正常组织分别为13.4%、16.7%,两者相比,P均〈0.01。IGF-1R、IGFBF-2的表达与NSCLC临床分期及淋巴结转移密切相关（P均〈0.05）。结论 IGF-1R、IGFBP-2在NSCLC组织中呈高表达,在NSCLC的发生、发展中发挥作用。     

食管鳞癌和异型增生中TGFβ_1表达的意义

食管鳞癌和异型增生中ＴＧＦβ１表达的意义邓登豪１罗金燕２朱海杭１李登銮１王康敏２１扬州大学医学院附属苏北医院消化病研究室江苏省扬州市２２５００１２西安医科大学第二临床医学院ＳｕｂｊｅｃｔｈｅａｄｉｎｇｓＥｓｏｐｈａｇｅａｌｎｅｏｐｌａｓｍｓＣａｒ...     

食管鳞癌组织中E—cadherin、VEGF的表达变化及意义

目的观察食管鳞癌组织中上皮性钙黏附蛋白（E—cadherin）和血管内皮生长因子（VEGF）的表达变化,并探讨其临床意义。方法采用免疫组化sP法检测60例食管鳞癌组织和癌旁正常组织中的E-cadherin、VEGF。结果食管鳞癌组织中E—cadherin表达阳性34例（56．6％）、VEGF表达阳性42例（70．0％）,癌旁正常组织中分别为55例（91．6％）、24例（40．0％）,两组比较,P均〈0．05。E-cadherin、VEGF表达与食管鳞癌临床分期、肿瘤浸润深度及淋巴结转移有关（P均〈0．05）。结论食管鳞癌组织中E—cadherin表达降低,VEGF表达升高;二者与食管鳞癌的浸润、转移有密切关系。     

食管鳞癌组织中cyclin D1和cyclin E的表达及意义

采用免疫组化法检测62例食管鳞癌组织中的细胞周期素（cyclin）D1、cyclin E,二者的阳性表达率分别为54.8%（34/62）、40.3%（25/62）,其表达与肿瘤长径、浸润深度、淋巴结转移、pTNM分期、肿瘤分化程度有关（P均〈0.05）;cyclin D1阳性表达组中cyclin E表达的阳性率高于cyclin D1阴性表达组（P〈0.05）;cyclin D1或cyclin E高表达的患者术后3 a生存率明显低于低表达者（P〈0.05）。认为cyclin D1和cyclin E是食管鳞癌预后不良的指标。     

畸胎瘤细胞源性生长因子和血管内皮生长因子在食管鳞癌中的表达及临床意义

目的 探讨食管鳞癌(ESCC)中畸胎瘤细胞源性生长因子(PCDGF)、血管内皮生长因子(VEGF)的表达与肿瘤临床病理参数之间的关系,明确PCDGF和VEGF在血管生成中的作用.方法 以免疫组化方法检测郑州大学第一附属医院2005年7月至2006年5 月收治的50例食管鳞癌患者手术切除标本PCDGF与VEGF的表达,并以CD105抗体标记肿瘤组织血管内皮细胞,计算肿瘤间质微血管密度(MVD).结果 食管鳞癌中PCDGF、VEGF的表达较正常食管上皮明显增加(P＜0.01);PCDGF和VEGF与肿瘤的浸润深度、TNM分期和淋巴结转移呈正相关(P均＜0.05);PCDGF、VEGF的表达与MVD值呈显著正相关(P＜0.01);PCDGF的表达与VEGF的表达呈正相关(P＜0.05).结论 PCDGF标记癌组织的敏感性较高,有望成为一种新的食管鳞癌肿瘤标志物.食管鳞癌中PCDGF、VEGF的表达与血管生成关系密切,可能通过促进肿瘤新生血管生成参与肿瘤的生长、浸润和转移.     

喉癌组织中VEGF-C及其受体VEGFR-3和D2-40的表达及意义

目的 观察血管内皮生长因子C（VEGF-C）及其受体（VEGFR-3）和D2-40在喉癌组织中的表达情况,探讨其在喉癌淋巴道转移过程中的作用及可能机制.方法 选择喉癌患者的癌组织、癌旁正常组织标本各40份,同期选择正常喉组织标本19份作对照.采用免疫组织化学法检测各标本中VEGF-C、VEGFR-3和D240的表达.结果 VEGF-C、VEGFR-3及D2-40在喉癌组织、癌旁组织及正常喉组织中均有表达,且其表达强度呈下降趋势（H分别为38.400、32.502,P均＜0.01）;在喉癌组织中,VEGF-C、VEGFR-3及D2-40的表达与淋巴转移、临床分期及临床分型有关（P均＜0.05）,与病理分级、肿瘤大小、吸烟量、年龄和性别无关（P均＞0.05）.喉癌组织中VEGF-C与VEGFRd的表达呈正相关（r=0.882,P＜0.01）.结论 VEGF-C、VEGFR-3及D2-40在喉癌组织中的表达均明显高于癌旁组织及正常喉组织,其高表达可能与喉癌的发生、发展有关.     

食管鳞癌组织中STAT3蛋白的表达及临床意义

目的 探讨食管鳞癌组织和癌旁正常黏膜组织中信号转导子和转录激活子3（STAT3）的表达及与食管鳞癌发生发展的关系.方法 应用免疫组化SP法检测122例食管鳞癌及其癌旁正常黏膜组织中STAT3蛋白的表达.结果 食管鳞癌组织中STAT3蛋白表达阳性率为89.3%,明显高于癌旁正常黏膜组织的77%（P＜0.05）.Ⅰ级、Ⅱ级、Ⅲ级食管鳞癌组织中STAT3蛋白的阳性率分别为73.7%、89.5%和100%,Ⅲ级中STAT3蛋白的阳性率显著高于Ⅰ级（P＜0.05）.浸润至深层（深肌层和外膜）的食管鳞癌组织中STAT3蛋白阳性表达率为92.8%,明显高于浸润至浅层（黏膜和浅肌层）食管鳞癌组织的76%（P＜0.05）.STAT3的表达与淋巴结转移无关（P＞0.05）.结论 STAT3蛋白过度表达与食管鳞癌的发生发展及恶性演进有关,STAT3有望成为评估食管癌预后的一个新标志物.     

食管鳞癌组织中p34^cdc2的表达变化及意义

目的观察人食管鳞癌组织中细胞分裂周期蛋白p34^cdc2的表达,并探讨其临床意义。方法利用组织芯片技术结合免疫组化及蛋白免疫印迹法检测138例食管癌患者肿瘤组织和配对正常食管黏膜组织中的p34^cdc2蛋白。结果p34^cdc2在食管鳞癌组织的表达明显高于配对正常黏膜组织,P〈0.01。p34^cdc2表达与食管鳞癌临床分期、淋巴结转移有关（P均〈0.05）,与分化程度和肿瘤浸润深度等无关（P均〉0.05）。结论食管癌组织中p34^cdc2表达升高。p34^cdc2可促进食管癌的发生与发展。     

Clinicopathological significance of vascular endothelial growth factor-C and cyclooxygenase-2 in esophageal squamous cell carcinoma

BACKGROUND: Vascular endothelial growth factor-C (VEGF-C) is a specific growth factor of lymphatics, which is known to play some role in tumor growth and metastasis to lymph nodes and distant organs in various malignancies. The purpose of the present study was to investigate the expression of VEGF-C in human esophageal squamous cell carcinomas (ESCC) to elucidate its role in tumor progression and lymph node metastasis. Another aim of the study was to investigate the relation between VEGF-C and cyclooxygenase-2 (COX-2) in ESCC. METHODS: The expression of VEGF-C and COX-2 in ESCC was evaluated in 13 endoscopic mucosal resection specimens and in 21 surgical specimens by immunohistochemical staining. Clinical data were obtained from medical records. RESULTS: The degree of VEGF-C expression increased as the depth of primary tumor progressed (r = 0.521, P = 0.002), the stage progressed (r = 0.572, P < 0.001), and the degree of COX-2 expression increased (r = 0.387, P = 0.024). The VEGF-C positive rate was different between early cancers in which regional lymph node metastasis was thought to be absent and advanced cancers in which regional lymph node metastases were confirmed after surgery (20.0% vs 100.0%; P < 0.001). CONCLUSIONS: The VEGF-C expression in ESCC is related to COX-2 expression, and VEGF-C is also associated with the depth of primary tumor, the stage, and probably lymph node metastasis. Thus the investigation of VEGF-C expression in ESCC may assist in management planning.     

Risk factors of lymph node metastasis in T1 esophageal squamous cell carcinoma

Background and Aim: To perform endoscopic mucosal resection (EMR) for T1 esophageal cancer, it is essential to estimate the lymph node status exactly. In order to evaluate the feasibility of EMR for esophageal cancers, we evaluated the clinicopathological features of T1 esophageal squamous carcinomas with an emphasis on the risk factors and distribution patterns of lymph node metastasis. Methods: From 1994 to 2006, a total of 200 patients with T1 esophageal carcinoma were treated surgically in our institution. Among them, clinicopathological features were evaluated for 197 consecutive patients with T1 squamous cell carcinoma. Results: The frequency of lymph node involvement was 6.25% (4/64) in mucosal cancers and 29.3% (39/133) in submucosal cancers (P < 0.001). In patients with M1 (n = 32) and M2 (n = 14) cancers, no lymph node metastasis was found. In multivariate analysis, size larger than 20 mm, endoscopically non‐flat type, and endo‐lymphatic invasion were significant independent risk factors for lymph node metastasis. The differentiation of tumor cell was not a risk factor for lymph node metastasis. Conclusions: We suggest that EMR may be attempted for flat superficial squamous esophageal cancers smaller than 20 mm. After EMR, careful histological examination is mandatory.     

High expression of PDGFA predicts poor prognosis of esophageal squamous cell carcinoma

Platelet-derived growth factor A (PDGFA), the most known member of PDGF family, plays a crucial role in occurrence and progression of different tumors. However, PDGFA expression and its clinical significance in esophageal squamous cell carcinoma (ESCC) are not clear. The present study aimed to assess the expression and prognostic value of PDGFA in ESCC.The Gene Expression Omnibus databases ({"type":"entrez-geo","attrs":{"text":"GSE53625","term_id":"53625"}}GSE53625, {"type":"entrez-geo","attrs":{"text":"GSE23400","term_id":"23400"}}GSE23400, and {"type":"entrez-geo","attrs":{"text":"GSE67269","term_id":"67269"}}GSE67269) and fresh clinical samples were employed for detecting PDGFA messenger RNA expression in ESCC. The associations of PDGFA expression with clinicopathological characteristics were evaluated by chi-square test. Kaplan–Meier analysis and Cox proportional hazard regression model were performed to determine the prognostic value of PDGFA in ESCC patients. PDGFA-related signaling pathways were defined by gene set enrichment analysis based on Gene Expression Omnibus databases.The PDGFA messenger RNA expression was upregulated in ESCC tissues compared with paired adjacent noncancerous tissues (P < .05) and was positively correlated with T stage (P < .05). Kaplan–Meier survival analysis suggested that ESCC patients with high PDGFA expression were associated with poorer overall survival compared to those with low PDGFA expression (P < .05), especially in advanced T stage (P < .05). Cox analyses showed that high expression of PDGFA was an independent predictor for poor prognosis in ESCC patients. Gene set enrichment analysis identified 3 signaling pathways (extracellular matrix receptor interaction, focal adhesion, and glycosaminoglycan biosynthesis chondroitin sulfate) that were enriched in PDGFA high expression phenotype (all P < .01).PDGFA may serve as an oncogene in ESCC and represent an independent molecular biomarker for prognosis of ESCC patients.     

HIF-1α基因沉默对食管鳞癌细胞功能性基因的影响

目的观察食管鳞癌细胞中缺氧诱导因子-1α（HIF-1α）基因与血管内皮生长因子（VEGF）、血红素加氧酶（HO-1）、基质金属蛋白酶-2（MMP-2）基因之间的关系及其对细胞周期的影响。方法以HIF-1α基因沉默的Eca-109细胞、化学模拟缺氧细胞及未干预细胞为研究对象,通过Western blot检测VEGF、HO-1、MMP-2基因在三种细胞中的表达差异以了解其与HIF-1α基因的关系,并通过流式细胞术分析了解HIF-1α基因沉默后细胞周期的变化。结果Western blot检测发现,同空白及模拟缺氧组比较,HIF-1α基因沉默后HIF-1α蛋白表达明显下调,同时VEGF、HO-1、MMP-2的蛋白表达均出现了明显下降。流式细胞分析表明,HIF-1α基因沉默后的Eca-109细胞组同对照组相比G1、G0期细胞明显增加,G2、M期细胞变化不大,S期细胞比例明显减少。结论HIF-1α与上述三种基因存在明显相关性,进而可能影响着食管鳞癌的血管生成、侵袭、应激保护等生物学行为,HIF-1α沉默可将食管鳞癌细胞阻滞于G1、G0期。     

Identification of EGFR and KRAS mutations in Chinese patients with esophageal squamous cell carcinoma

The prognosis of esophageal squamous cell carcinoma (ESCC) is poor. It is urgent to improve this situation. Epidermal growth factor receptor (EGFR)‐targeted therapy possesses a promising clinical efficacy. Mutations of EGFR and V‐Ki‐ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) have been identified in esophageal carcinoma, but corresponding Chinese data are limited. So we investigated the mutation status of EGFR and KRAS in Chinese patients with ESCC, and explored their correlations with clinicopathological features. Formalin‐fixed paraffin‐embedded surgically resected tumor samples were obtained from 50 randomly selected Chinese patients with ESCC. EGFR mutations in exons 18–21 were detected by Scorpions amplification refractory mutation system technology. KRAS mutations in codons 12, 13 were detected by direct sequencing of polymerase chain reaction products. The correlations between clinicopathological features and the mutation status of EGFR and KRAS were analyzed using the Statistical Package for the Social Sciences. In the present study, EGFR mutations were found in 7 (14%) out of 50 patients, including G719X missense mutation (n= 1), in‐frame deletion (n= 2), and L858R missense mutation (n= 5). Six (12%) out of 50 patients had KRAS mutations in codon 12. Concurrent EGFR and KRAS mutations were detected in one sample. The presences of EGFR and KRAS mutations were not associated with gender, age, smoking history, cell differentiation, or cancer stage. In conclusion, the incidence of EGFR mutations in Chinese patients with ESCC was higher than that of previous reports, and the incidence of KRAS mutations was not low. EGFR and KRAS mutations were mainly located in exons 19 and 21 and codon 12, respectively. Unlike in NSCLC, concurrent EGFR and KRAS mutations existed.     

食管鳞癌组织中JWA、FAK表达变化及其与淋巴结转移的关系

目的观察食管鳞癌组织中JWA蛋白和黏着斑激酶（FAK）的表达变化,并探讨其与食管鳞癌淋巴结转移的关系。方法采用蛋白免疫印迹法检测37例食管鳞癌患者肿瘤组织及其癌旁组织中的JWA、FAK蛋白。结果食管鳞癌组织与癌旁组织中JWA蛋白的相对表达量分别为0.302±0.119、0.638±0.128,FAK分别为0.717±0.153、0.432±0.097,二者JWA、FAK蛋白表达量相比,P均〈0.05。有、无淋巴结转移者JWA蛋白相对表达量分别为0.163±0.37、0.383±0.06,FAK蛋白分别为0.832±0.134、0.658±0.109,P均〈0.05。JWA、FAK蛋白在食管鳞癌组织中的表达呈负相关（r=-0.736,P〈0.01）。结论食管鳞癌组织中JWA蛋白表达下调,FAK蛋白表达上调,且其表达变化与食管鳞癌淋巴结转移有关。JWA可能通过抑制FAK的表达,发挥抑制食管鳞癌淋巴结转移的作用。