Expression of vascular endothelial growth factor in hepatocellular carcinoma and the surrounding liver: correlation with angiographically assisted CT

OBJECTIVE: The purpose of our study was to assess the correlation between the intensity and characteristics of contrast enhancement on angiographically assisted CT and the intensity of vascular endothelial growth factor (VEGF) expression in hepatocellular carcinoma (HCC) and in the surrounding nontumorous liver. MATERIALS AND METHODS: The intensity of VEGF expression in HCC and in the surrounding liver was expressed as a VEGF expression index by Western blot analysis in 20 surgical specimens resected in 20 patients between March 2000 and August 2002. Findings on CT during arterial portography (n = 20) and CT hepatic arteriography (n = 17) were retrospectively evaluated to determine contrast enhancement indexes and the enhancement characteristics of HCCs and of the surrounding liver. Contrast enhancement indexes and VEGF expression indexes were correlated using a simple regression test, and enhancement characteristics and VEGF expression indexes were correlated using the Spearman's rank correlation test. RESULTS: On CT hepatic arteriography, the contrast enhancement indexes of HCCs showed moderate inverse correlation with the VEGF expression indexes of HCCs (r = -0.57, p = 0.017) and high inverse correlation with the differences between the VEGF expression indexes of HCCs and those of livers (difference in the VEGF expression index, -0.80; p = 0.0001). The contrast enhancement index of the liver showed marginal moderate direct correlation with the VEGF expression index of the liver (0.44, p = 0.076) and high inverse correlation with the difference in the VEGF expression index (-0.71, p = 0.0013). On CT during arterial portography, the contrast enhancement indexes of HCCs showed moderate inverse correlation with the difference in the VEGF expression index (-0.51, p = 0.023). The qualitative degree of heterogeneity of hepatic artery enhancement in HCC on CT hepatic arteriography showed moderate direct correlation with the VEGF expression indexes of HCCs (0.55, p = 0.033) and high direct correlation with the difference in the VEGF expression indexes (0.73, p = 0.004). CONCLUSION: Our results indicated that the intensity and heterogeneity of hepatic artery enhancement of HCCs on CT hepatic arteriography correlated with the degree of VEGF expression in HCCs.     

肝癌患者血浆血管内皮生长因子的表达及动脉化疗栓塞对其影响的初步研究

目的　研究血管内皮生长因子 (vascularendothelialgrowthfactor,VEGF)在肝细胞癌(hepatocellularcarcinoma ,HCC)患者血浆中的表达水平与肝癌临床病理特征间的关系及其在动脉化疗栓塞 (transarterialchemoembolization ,TACE)治疗前后的变化。方法　 4 5例临床诊断为HCC的患者 ,于TACE术前、术后 1、3、7d及 1个月抽血 ,用酶联免疫吸附测定法 (ELISA法 )定量检测血浆中VEGF水平 ,同时对 2 0例肝脏良性疾病患者及 17例健康人血浆中VEGF水平进行检测。结果　HCC组血浆VEGF表达水平明显高于肝脏良性疾病组 (P =0 0 0 6 )及健康对照组 (P =0 0 0 3)。血浆VEGF表达水平随HCC患者TNM分级的升高而逐步升高 (P =0 0 4 4 ) ,较高血浆VEGF表达见于肿瘤较大 (P =0 0 0 6 ) ,以及并发有门脉癌栓 (P =0 0 11)、远处转移 (P =0 0 17)或动 门脉瘘 (P =0 0 2 6 )的病人。血浆VEGF的水平与血小板水平弱相关 (r=0 312 ,P =0 0 38) ,与血清甲胎蛋白 (AFP)水平不相关 (r =0 0 6 8,P =0 6 5 8)。TACE术后 1d血浆VEGF水平明显升高 ,与术前相比差异有显著性意义 ;其后 3、7d逐渐下降 ,与术前相比差异无显著性意义。血浆VEGF变化率 (术后 1个月 /术前× 10 0 % )与患者碘油积聚 (rs=0 4 94 ,P =0 0 0 1)及病灶变     

Angiogenesis in hepatocellular nodules: correlation of MR imaging and vascular endothelial growth factor

PURPOSE: To assess the correlation between magnetic resonance (MR) imaging findings and angiogenetic activity in hepatocellular nodules evaluated by immunohistochemical staining with antibody of vascular endothelial growth factor (VEGF). MATERIALS AND METHODS: We searched the pathologic records of our institution from December 1999 to April 2002, and included 16 patients with hepatocellular carcinoma (N = 14), large regenerative nodule (N = 1), and dysplastic nodule (N = 1) who underwent orthotopic liver transplantation (10 patients) or partial hepatectomy (six patients) and MR imaging within an interval of two weeks. The MR images were retrospectively assessed qualitatively and quantitatively. Angiogenetic activity of the hepatic nodules was evaluated by means of immunohistochemical study for VEGF. Analysis of variance and the Scheffé criterion were used for statistical evaluation. RESULTS: Hepatic nodules with moderate to strong immunoreactivity for VEGF showed higher signal intensity on T1-weighted images (P < 0.05) and those with intense immunoreactivity for VEGF showed higher signal intensity on T2-weighted images (P < 0.05). No correlation was found between the immunoreactivity for VEGF and tumor vascularity on postcontrast early- and late-phase images. CONCLUSION: Our current results suggest that signal intensity on unenhanced T1- and T2-weighted MR images may correlate with immunoreactivity for VEGF. Correlation was not found between immunoreactivity for VEGF and signal intensity on gadolinium-enhanced MR images.     

血管内皮生长因子表达与输尿管癌的生物学行为关系

 目的在分子水平上了解原发性输尿管癌生长、发展的机制。方法 应用免疫组化技术一两步法,测定26例原发性输尿管癌组织的血管内皮生长因子(Vascular endothelial growth factor,VEGF)表达。结果 26例肿瘤组织中VEGF阳性表达16例(61.54％),显著高于正常输尿管组织及输尿管息肉(P＜0.01)。VEGF在原发性输尿管癌中的表达,Ⅲ级高于Ⅰ、Ⅱ级(P＜0.05),B以上高于T2以下(P＜0.05)。VEGF阳性组术后5a复发率明显高于阴性组(P＜0.01),5a生存率明显低于阴性组(P＜0.05)。结论VEGF蛋白表达与原发性输尿管癌的临床分期、病理分级及患者的预后相关。     

血管内皮生长因子在原发性肝癌中的诊断及预后意义

血管内皮生长因子(VEGF)是血管形成的重要调节因子,参与肿瘤的形成及发展的多个过程.VEGF特异性作用于血管内皮细胞,有促进新生血管形成、增加血管通透性、促进细胞迁移和抑制核因子kB活化等生物学功能.原发性肝癌恶性程度高,预后差,其生理学特性与VEGF作用相关.现就VEGF的结构、功能及其与肝癌的诊断及预后予以综述.     

肝细胞癌螺旋CT扫描与血管内皮生长因子表达的相关性研究

 目的 探讨肝细胞癌(HCC)组织中血管内皮生长因子(VEGF)的表达水平与螺旋CT增强扫描表现关系,从影像学角度评价VEGF在HCC表达的意义与特点.方法 50例外科手术切除、病理证实的HCC患者,术前均作肝脏的平扫与双期增强扫描,依据肿瘤的强化方式分为四型:动脉期强化型、门静脉期强化型、双期强化型及双期不强化型.采用流式细胞技术测定手术标本肿瘤边缘区、肿瘤中央区及肿瘤临界区的VEGF表达水平.结果 ①HCC肿块边缘区VEGF的表达水平高于肿瘤中央区和临界区(P＜0.01).②VEGF的表达水平与HCC分级存在正相关性(P＜0.01).③HCC分型与VEGF表达水平相关(P＜0.05).4、HCC动脉期肿块强化CT值与VEGF表达水平正相关(P＜0.01).5、HCC肿块的大小与VEGF表达水平无关(P＞0.05).有淋巴结转移及门静脉癌栓形成的病例其VEGF表达水平高于无淋巴结转移、无门静脉癌栓形成的病例.(P＜0.01,P＜0.05).结论 HCC肿瘤动脉期强化值与VEGF表达水平均值呈线性相关(r=0.713),且VEGF表达水平与HCC分型、分级、肿瘤的强化方式及肿瘤是否转移密切相关.     

肝细胞癌CT表现与手术病理对照及其与血管内皮生长因子表达的关系

目的：探讨肝细胞癌(HCC)的 CT 表现与手术病理对照及其与血管内皮生长因子(VEGF)表达的关系,为治疗提供依据。方法收集75例 HCC 患者资料,术前行 CT 平扫及增强扫描,术后对病理标本进行石蜡包埋、组织切片,常规 HE 染色,并采用免疫组织化学染色 S-P 法,检测其 VEGF 蛋白的表达。将 HCC 的 CT 表现与手术病理进行对照,并统计分析 CT 所见与 VEGF表达的关系。结果①75例 HCC 患者,术前 CT 所表现的肝硬化和淋巴结肿大与手术病理所见差异有统计学意义(P <0.05);而HCC 的肿瘤长径、门静脉或肝静脉癌栓的 CT 表现与手术病理所见相似,差异无统计学意义(P >0.05)。②HCC 的假包膜、肿瘤长径、病理血管、瘤内坏死与 VEGF 表达之间差异有统计学意义(P <0.05);HCC 的门静脉或肝静脉癌栓、肝硬化、肝内病灶(单发或多发)、淋巴结肿大与 VEGF 表达之间差异无统计学意义(P >0.05)。结论 HCC 的 CT 表现与 VEGF 表达密切相关,CT 征象虽然可以大部分反映 HCC 的病理及生物学特性,仍有一定的局限性。     

血管内皮生长因子在胃癌中的 表达及其临床意义

目的探讨胃癌中人表皮生长因子受体2(human epidermal growth factor receptor 2,HER2)和血管内皮生长因子(vascular endothelial growth factor,VEGF)的表达与胃癌的发生、发展的关系,及作为分子靶点指导胃癌患者临床用药的意义。方法采用免疫组化(immunohistochemistry,IHC)的方法检测103例胃癌患者HER2及VEGF的状态,同时联合荧光原位杂交的方法检测HER2的状态,并与患者的临床资料进行相关性分析。结果①胃癌中HER2扩增率约为11%(11/103),在阳性病例中IHC与荧光原位杂交(fluorescentin situ hydridization,FISH)方法的符合率为90%,具有相关性(P<0.01);②HER2的扩增与胃癌的病理分级、淋巴结转移与否及Lauren分型相关(P<0.05);③胃癌中VEGF表达阳性率约为24%(25/103),VEGF的阳性表达与肿瘤的浸润深度、病理分级、Lauren分型相关(P<0.05);④HER2的表达与VEGF的表达不相关(P>0.05)。结论 HER2、VEGF的阳性表达与胃癌特别是分化较好的胃管状腺癌的发生、发展密切相关。联合检测HER2及VEGF在胃癌(特别是肠型胃癌)中的表达对了解胃癌的发生、发展,及靶向药物曲妥珠单抗和贝伐单抗的选择具有重要意义。     

反义寡核苷酸抑制肝癌细胞血管内皮生长因子的表达

目的：研究血管内皮生长因子(VEGF)反义寡核苷酸(ODN)对人肝癌细胞系VEGF表达的抑制作用，探讨肝癌基因治疗的新方法。方法：人肝癌细胞系SMMC7721能表达VFGF，采用人工合成反义、正义ODN分别作用于SMMC7721细胞，RT—RCR、流式细胞仪比较各处理组VFGF mRNA及其蛋白的表达变化情况。结果：VEGF RT—PCR扩增条带的图像分析平均灰度值显示，反义组为0．4379，正义组为0．7367，对照组为0．7462。流式细胞仪分析VFGF蛋白表达率，反义组为17．2％，正义组为31．8％，对照组为31．2％。结论：反义ODN能够抑制人肝癌细胞的表达，其有望成为抗肝癌的新一代基因治疗药物。     

血管内皮生长因子与肝癌肝动脉灌注化疗栓塞术

血管内皮生长因子在肝细胞肝癌血管生成的调控中起着关键性作用，经肝动脉灌注化疗栓塞术是不能手术肝癌患者最有效的姑息性治疗方法之一。本文从如下方面综述血管内皮生长因子肝癌肝动脉灌注化疗栓塞术的关系：①血管生成与血管内皮生长因子的关系；②血管内皮生长因子在肝癌中的表达；③肝癌的经肝动脉灌注化疗栓塞术治疗对血管内皮生长因子的影响；④抗血管生成策略与肝动脉灌注化疗栓塞术治疗的关系。     

肝动脉化疗栓塞对肝癌肿瘤新生血管生成及血管内皮细胞生长因子表达的影响

目的研究肝细胞癌(hepatocellularcarcinoma,HCC)经导管动脉化疗栓塞(transcatheterarterialchemoembolization,TACE)后残癌组织微血管密度(microvesseldensity,MVD)、微血管直径、血管内皮细胞生长因子(vascularendothelialgrowthfactor,VEGF)的表达情况及其意义。方法经病理证实的HCC63例,包括单纯手术切除42例(对照组),TACE术后行Ⅱ期手术切除21例(TACE组)。TACE组患者手术前接受1~2次不等的TACE治疗,均按统一规范标准给予化疗药物灌注+栓塞治疗。对手术切除标本进行免疫组织化学染色,其中TACE组取病灶边缘残存肿瘤部分,检测肿瘤组织的MVD、微血管直径及肿瘤细胞VEGF的表达。结果对照组MVD值为(5169±1817)条,TACE组MVD值为(5857±1575)条,二者之间比较差异无统计学意义(t=148,P>005);对照组微血管直径为(1762±1054)μm,TACE组微血管直径为(1579±765)μm,二者之间比较差异无显著性意义(t=071,P>005)。对照组VEGF阳性染色细胞数为13826±6524,TACE组VEGF阳性染色细胞数为24366±8888,二者之间比较差异有统计学意义(t=534,P<001),TACE显著上调了VEGF蛋白的表达;VEGF阳性染色细胞数与MVD明显相关(r=04936,t=44329,P<005)。结论化疗栓塞术后残癌组织存在丰富的肿瘤血供,残癌组织肿瘤细胞VEGF表达明显升     

3D dynamic contrast-enhanced MRI of rectal carcinoma at 3T: correlation with microvascular density and vascular endothelial growth factor markers of tumor angiogenesis

PURPOSE: To determine how dynamic contrast-enhanced (DCE) MRI at 3T correlates with rectal carcinoma angiogenesis. MATERIALS AND METHODS: Three-dimensional (3D) DCE MRI was performed in 38 patients (23 males, 15 females, mean age 60 years) with histologically-confirmed rectal carcinoma at 3T. Time-intensity curves (TICs) were used to measure peak enhancement ratio (ER(peak)), time to peak enhancement (T(peak)), first enhancement time (T(first-enhance)), and uptake rate for rectal tumor, normal rectal wall, and gluteal muscle. After tumor resection, microvascular density (MVD) and vascular endothelial growth factor (VEGF) expression were determined using immunohistochemistry (IHC) stains on available specimens (N = 24) to correlate with DCE MRI. RESULTS: Rectal carcinoma showed higher ER(peak) (3.0 +/- 0.9 vs. 1.9 +/- 0.9, P < 0.001), higher uptake rate (2.8 +/- 1.5/minute vs. 1.2 +/- 0.9/minute, P < 0.001), earlier T(peak) (88 +/- 56 seconds vs. 124 +/- 72 seconds, P = 0.027), and earlier T(first-enhance) (34 +/- 6 seconds vs. 40 +/- 7 seconds, P = 0.008) than normal rectal wall. Adenocarcinoma had shorter T(peak) compared to signet cell carcinoma (77 +/- 48 seconds vs. 160 +/- 62 seconds, P = 0.004). T(peak) was negatively correlated with MVD (r = -0.516, P = 0.01) and the mean T(peak) was significantly earlier for the VEGF-positive group compared to the VEGF-negative group (57 +/- 17 seconds vs. 107 +/- 64 seconds, P = 0.021). CONCLUSION: DCE MRI parameters help predict rectal tumor angiogenesis measured by MVD and VEGF expression and discriminate malignant from normal tissue.     

MRI findings of recurrent hepatocellular carcinoma after liver transplantation: preliminary results

Purpose

To describe the patterns of recurrence and serial magnetic resonance imaging (MRI) features of hepatocellular carcinoma (HCC) after liver transplantation.

Materials and Methods

All cases of recurrent HCC after transplantation between September 2002 and August 2009 that underwent MRI including precontrast T1, T2‐weighted images, and postgadolinium dynamic images were reviewed. On MRI we evaluated the characteristics and patterns of recurrent HCC after transplantation.

Results

A total 7 of 76 transplanted patients (four men, three women, age range, 45–63, mean 52.7 years) were included in this study. Four patients (57.1%) were identified to have a pattern of persistent local disease (PLD) near the transplanted liver, hepatorenal space, or suture site within 2.75 years (range, 2–4 years). Two patients showed recurrent HCC in the allograft alone within 5 years. One patient showed an intraperitoneal seeding (IPS) pattern which demonstrated diffuse peritoneal infiltration and thickening within 9 months. The diffuse metastatic disease (DMD) pattern was observed as a late manifestation of PLD and IPS. The most prominent volume of recurrent tumor burden was found in an extrahepatic (5 of 7 patients) compared to an intrahepatic (2 of 7 patients) location. The signal intensities and enhancement patterns did not exhibit change with disease progression.

Conclusion

We describe four patterns of recurrence of HCC following transplant. The most prominent tumor burden was located in an extrahepatic compared to an intrahepatic location. J. Magn. Reson. Imaging 2011;33:1399–1405. © 2011 Wiley‐Liss, Inc.     

胰腺导管癌组织中VEGF表达和肿瘤微血管计数的临床意义

目的探讨胰腺癌组织中血管内皮生长因子(VEGF)的蛋白表达、肿瘤微血管(MVD))计数与肿瘤临床病理学特征,研究胰腺肿瘤的预后因素。方法选择病理证实为胰腺导管腺癌且资料完整的48例石蜡切块标本,应用免疫组织化学的方法进行VEGF蛋白检测及MVD计数,与正常胰腺组织及癌旁组织对照,并结合病人临床病理资料进行分析。结果胰腺癌组织中VEGF表达阳性率为64．58％(31／48)。MVD计数为10～34个,中位数为21。VEGF蛋白表达与MVD计数有明显相关性(P＜0．01)。VEGF蛋白表达与肿瘤大小、淋巴结转移和肿瘤TNM分期都有相关性,肿瘤≥2cm比＜2cm的VEGF表达阳性率高(P＜O．05)。有淋巴结转移者VEGF表达阳性率高(P＜0．01)。肿瘤TNM分期Ⅲ～Ⅳ期比Ⅰ～Ⅱ期VEGF表达阳性率高(P＜0．05)。COX分析显示,VEGF蛋白表达及MVD计数与病人生成时间有关。VEGF表达阳性,死亡危险度大;MVD个数多者,死亡危险度大。结论血管生存在胰腺癌的发生、发展和转移过程中起着重要的作用,VEGF和MVD可作为评价胰腺癌预后的指标之一,抗血管治疗可能成为胰腺癌的一种新的治疗手段。     

表皮生长因子受体2和血管内皮生长因子在胃癌中的表达及其临床意义

目的探讨胃癌中人表皮生长因子受体2(human epidermal growth factor receptor 2,HER2)和血管内皮生长因子(vascular endothelial growth factor,VEGF)的表达与胃癌的发生、发展的关系,及作为分子靶点指导胃癌患者临床用药的意义。方法采用免疫组化(immunohistochemistry,IHC)的方法检测103例胃癌患者HER2及VEGF的状态,同时联合荧光原位杂交的方法检测HER2的状态,并与患者的临床资料进行相关性分析。结果①胃癌中HER2扩增率约为11%(11/103),在阳性病例中IHC与荧光原位杂交(fluorescentin situ hydridization,FISH)方法的符合率为90%,具有相关性(P<0.01);②HER2的扩增与胃癌的病理分级、淋巴结转移与否及Lauren分型相关(P<0.05);③胃癌中VEGF表达阳性率约为24%(25/103),VEGF的阳性表达与肿瘤的浸润深度、病理分级、Lauren分型相关(P<0.05);④HER2的表达与VEGF的表达不相关(P>0.05)。结论 HER2、VEGF的阳性表达与胃癌特别是分化较好的胃管状腺癌的发生、发展密切相关。联合检测HER2及VEGF在胃癌(特别是肠型胃癌)中的表达对了解胃癌的发生、发展,及靶向药物曲妥珠单抗和贝伐单抗的选择具有重要意义。     

血管内皮生长因子C在上皮性卵巢癌的表达与淋巴结转移的关系

目的 :了解上皮性卵巢癌的腹股沟和腹膜后淋巴结转移机制 ,观察具有介导淋巴管内皮细胞增殖和淋巴管增生的血管内皮生长因子C(VEGF -C)在上皮性卵巢癌中的表达。方法 :采用免疫组化染色 ,光镜观察结果并确定VEGF -C在良性、交界性及恶性上皮性卵巢肿瘤组织中的表达。结果 :在良性、交界性及恶性上皮性卵巢肿瘤组织中皆有VEGF -C的表达 ,但卵巢癌表达明显高于良性及交界性肿瘤 ,卵巢癌表达强度与腹膜转移及腹股沟和腹膜后淋巴结转移密切相关 ,与远处转移、病理类型、病理分级、临床分期、年龄等无关。结论 :VEGF -C在卵巢癌的表达上调有利于淋巴结转移的发生 ,此过程可能和肿瘤的淋巴管生成有关。VEGF -C的检测可作为预测卵巢癌淋巴道转移及判断预后的指标之一 ,对VEGF -C /VEGFR - 3信号通路的阻滞研究有望成为抗肿瘤淋巴管转移治疗新的有效手段。     

自发性高血压大鼠心肌血管内皮生长因子表达水平的检测

 目的探讨血管内皮生长因子(Vascular endothelial growth factor,VEGF)在自发性高血压大鼠(Spontaneously hyper-tensive rat,SHR)心肌细胞中的表达情况,分析其与高血压时心肌毛细血管稀少及微小动脉"重塑"(remodeling)的关系.方法应用免疫组化SP染色法及计算机图像分析技术,对幼年(6周,n=15)和成年(12个月,n=15)SHR大鼠及幼年(6周,n=10)和成年(12个月,n=10)同系正常血压对照组京都Wistar大鼠(Wistar-Kyoto,WKY)心肌VEGF蛋白的表达水平进行了定量分析.结果在4组大鼠心脏各部(心房肌、心室肌、房间隔、室间隔等)心肌细胞浆中及冠状动脉各级分支的血管平滑肌细胞中均见有阳性VEGF表达,6周龄、12个月龄WKY及6周龄SHR三组间表达水平差异无统计学意义(P＞0.05),而12个月龄SHR组表达水平较其他三组均高(P＜0.05).结论随着成年SHR大鼠血压的升高,心肌及血管平滑肌细胞中VEGF蛋白的表达水平上调,可能是对高血压所致的靶器官继发性毛细血管减少的一种代偿反应,高表达的VEGF可对抗由于缺氧诱导的内皮细胞凋亡,维持其存活,并促进微血管再生.     

经化疗栓塞治疗后肝细胞癌患者血清血管内皮生长因子与影像学特征的关系

目的　评估经导管化疗栓塞 (TACE)前后肝细胞癌患者血清血管内皮生长因子 (VEGF)水平变化及其与影像学的关系。方法　前瞻性对 30例肝细胞癌患者分别于第 1次TACE术前 1d、术后 3～ 4d及 2 8～ 30d测量血清VEGF水平。采用酶联免疫夹心法 (ELISA)定量测定血清VEGF水平。TACE术后 6个月CT及DSA评估患者肝癌转移发生情况。结果　在碘油分布不均匀及门静脉癌栓组中 ,术后血清VEGF水平与术前比较增高 (P <0 .0 5 )。转移性肝癌组患者术前的血清VEGF为 (2 11.0 6± 112 .11) pg/ml,显著高于非转移性肝癌组患者 (135 .79± 4 9.82 )pg/ml(P <0 .0 5 )。 结论　综合评价VEGF水平与影像学表现能较好的了解患者的预后。