Glut1、MVD在大肠癌的表达及与肝转移关系

[目的]探讨大肠癌组织中Glut1、MVD表达及其与肝转移的关系。[方法]采用免疫组化SP法,检测42例大肠癌组织中Glut1及MVD的表达。[结果]Glut1阳性表达率为91%,MVD值为15~145(43.2±25.4)。大肠癌组织中Glut1表达与MVD表达呈显著正相关(r=0.421,P<0.01)。两者均与肝转移和Dukes分期呈正相关(P<0.05,P<0.01),且在肝转移组中两者表达呈高度一致性,其表达一致率为84.2%,与非肝转移组(34.8%)比较有显著性差异(P<0.01)。[结论]Glut1、MVD与大肠癌恶性演进有关。Glut1、MVD共同检测有利于大肠癌患者肝转移的预测。     

大肠癌组织中血管内皮生长因子的表达及其临床意义

目的探讨大肠癌患者血管内皮生长因子(VEGF)与组织学分级和Dukes分期的关系.方法采用逆转录-聚合酶链反应(RT-PCR)的方法,检测了68例大肠癌患者肿瘤组织中VEGF表达水平.结果肿瘤组织中VEGF表达水平在不同组织学分级之间比较,无显著性差异;Dukes C、D期组显著高于Dukes A、B期.结论检测大肠癌患者VEGF的表达,可作为判断大肠癌分期、预测淋巴结转移和远处转移的1个指标.     

CD44V6、MVD在大肠癌组织中的表达及其与肝转移和预后的关系

目的　探讨大肠癌组织中CD 44V 6、MVD表达及其与大肠癌的临床病理因素、肝转移和预后的关系。方法　采用免疫组化SABC法 ,检测 5 1例大肠癌组织中CD 44V 6及MVD的表达情况。结果　CD44V 6阳性表达率为 76.5 % ,MVD值为 10～15 2 (4 4 .8± 2 8.1)。大肠癌组织中CD 44V 6表达与MVD表达呈显著正相关 (γ =0 .43 3 ,P <0 .0 1)。两者均与淋巴结转移、肝转移及Dukes分期呈正相关 (P <0 .0 5 ,P <0 .0 1) ,且在肝转移组中两者表达呈高度一致性 ,其表达一致率为 85 .7% ,与非肝转移组(3 3 .3 % )比较 ,有非常显著性差异 (P <0 .0 1)。CD 44V 6、MVD是影响大肠癌预后的独立因素 ,两者均高度表达者的预后差。结论CD 44V 6、MVD与大肠癌浸润转移及恶性程度呈正相关。大肠癌组织中CD44V 6表达与MVD表达呈正相关。CD44V 6、MVD共同检测有利于预测大肠癌患者肝转移和预后     

MK、CD105及VEGF在大肠癌组织中的表达及其临床意义

目的探讨MK、CD105和VEGF的表达与大肠癌生物学行为的关系及对预后的意义。方法采用免疫组织化学方法检测50例大肠癌组织MK、CD105和VEGF表达水平,并对其与大肠癌临床病理特征的关系进行统计学分析。结果本组50例大肠癌组织中,MK阳性表达率为72%,VEGF的阳性表达率为64%,MK和VEGF均为阳性时CD105标记的大肠癌组织MVD值(73.87±6.13)明显高于MK和VEGF均为阴性组的MVD值(62.94±6.99)(P<0.01)。三者的表达均与大肠癌的Dukes分期、淋巴结转移、浸润深度有关。结论MK的阳性表达与大肠癌的发生、发展和预后密切相关,可联合VEGF和CD105作为1组有价值的肿瘤标记和预后指标。     

大肠癌组织COX-2和Ki-67及MVD表达与肝转移相关性的研究

目的:研究COX-2、Ki-67和微血管密度(MVD)在大肠癌组织中的表达及其相互关系,探讨影响大肠癌肝转移的因素.方法:回顾性分析56例大肠癌肝转移病例的临床病理特征,并取56例无肝转移病例作对照.用免疫组织化学方法检测大肠癌标本中COX-2、Ki-67的表达和MVD,分析三者之间及其与临床病理因素的相关性.用单因素和多因素分析研究影响大肠癌肝转移的相关因素.结果:本组大肠癌COX-2蛋白阳性率为91.1%,Ki-67 LI为(44.1±15.0)%,MVD平均为(42.1±9.5)/高倍视野.大肠癌组织中COX-2、Ki-67 LI和MVD相互之间具有极强的相关性,并且三者都与肿瘤的Duke分期和肝转移密切相关.多因素Logistic回归分析发现,Duke分期、浸润深度、腹水、COX-2表达和MVD是大肠癌肝转移最重要的5个影响因素.结论:Duke分期、浸润深度、腹水、COX-2表达和MVD是大肠癌肝转移的5个独立影响因素,常规检测临床和生化指标有助于早期发现大肠癌肝转移.     

大肠癌组织中血管内皮生长因子的表及其临床意义

目的：探讨大肠癌组织中血管内皮生长因子（VEGF）与组织学分级和Dukes分期的关系。方法：采用逆转录－聚合酶链反应（RT－PCR）的方法,检测了68例大肠癌患者肿瘤组织中VEGF表达水平。结果：肿瘤组织VEGF表达表达水平在不同组织学分级之间比较,无显著性差异;DukesC、D期组显著高于DukesA、B期。结论：检测大肠癌患者VEGF的表达,可作为判断大肠癌分期、预测淋巴结转移和远处转移的1个指标。     

肝细胞癌组织中VEGF、MMP-2和MVD的表达及其相关性研究

[目的]研究肝细胞癌(HCC)组织中血管内皮生长因子(VEGF)及基质金属蛋白酶-2(MMP-2)蛋白的表达及其临床意义,并探讨其与血管生成的关系.[方法]采用免疫组化法检测60例肝癌组织及癌旁肝组织中VEGF及MMP-2的表达,用CD34标记免疫组化法检测微血管密度(MVD).[结果]VEGF及MMP-2在癌组织中的阳性率分别为63.33%和60.00%,而在癌旁组织中的阳性率分别为33.33%和26.67%,癌组织与癌旁组织比较差异有显著性(P＜0.01).癌组织的MVD为54.92±8.55,癌旁组织的MVD为21.36±6.63,两者差异有显著性(P＜0.01).VEGF在人肝癌组织中的表达与术后复发、肝外转移、临床分期、门静脉癌栓、肿瘤直径相关.MMP-2在人肝癌组织中的表达与临床分期、门静脉癌栓、肝外转移及术后复发相关.在癌组织中MVD与VEGF及MMP-2的表达呈正相关,VEGF与MMP-2的表达亦呈正相关.[结论]HCC中VEGF及MMP-2的高表达与肿瘤血管形成有关,在HCC的发生、发展及术后复发过程中起重要作用.     

大肠癌患者外周血癌细胞CK20检测及其意义

目的:探讨大肠癌患者外周血癌细胞角蛋白20(cytokeratin,CK20)检测与转移复发的关系。方法:以非同位 素RT-PCR方法,检测30例大肠癌患者术前和术后外周血中大肠癌细胞的标志物CK20,同时检测20例健康者外周血作对 照。结果:30例患者外周血中查出CK20阳性表达23例,阳性率76.67%,20例健康者外周血均无CK20表达。CK20阳性检 出与Dukes分期、淋巴结转移和肝转移存在显著性差异(P<0.05),术后3天内外周血CK20阳性检出较术前多出2例。随访 发现,外周血CK20扩增阳性者,术后发生肝转移的机会增加(33.3%)。结论:检测大肠癌患者外周血微转移癌细胞CK20可 提高大肠癌临床分期的准确性,帮助综合判断患者的预后,且可能有助于早期诊断大肠癌肝脏微小转移。     

卵巢肿瘤组织中血管内皮生长因子表达和微血管密度与其临床病理的关系

 目的　探讨卵巢肿瘤组织中VEGF表达和MVD与其临床病理的关系。方法　对 5 4例卵巢恶性肿瘤及对照采用SABC免疫组织化学法测定其VEGF表达和MVD。结果　 (1)恶性肿瘤组织中的VEGF表达和MVD明显高于良性肿瘤和正常卵巢组织 (P <0 .0 1)。 (2 )恶性肿瘤中有肝转移者 ,其MVD明显高于无肝转移者 (P <0 .0 5 )。 (3)恶性肿瘤组织中VEGF阳性表达和MVD丰富者的平均总生存期虽短于VEGF阴性表达和MVD不丰富者。但二者累积生存率均无显著性差异 (P >0 .0 5 )。结论　恶性肿瘤组织中的VEGF阳性表达和MVD明显增高并与是否出现肝转移灶呈正相关 ,但与其它临床病理及预后的相关性尚待确定。     

VEGFR-2、MVD在大肠癌组织的表达及其临床意义

目的:探讨血管内皮细胞生长因子受体-2(VEGFR-2)及微血管密度(MVD)在大肠癌组织中的表达与大肠癌生物学行为之间的关系。方法:采用免疫组化SP方法,检测54例大肠癌组织、18例癌旁正常组织中VEGFR-2的表达,以CD34标记血管内皮细胞,对CD34阳性血管进行MVD计数。结果:VEGFR-2在大肠癌组织中的阳性表达率为59.26%,在癌旁正常组织中阳性表达率为22.22%,差异有统计学意义(P<0.05)。VEGFR-2的表达与大肠癌浸润深度、淋巴结转移、远处转移、临床分期呈正相关(P<0.05)。大肠癌组织中VEGFR-2阴性表达者5年总生存期明显高于VEGFR-2阳性表达组(分别为48.97%及20.64%,P<0.05)。大肠癌组织、癌旁正常组织中MVD分别为(28.57±9.41个/HP、10.53±3.94个/HP),二者比较差异有统计学意义(P<0.01)。MVD与浸润深度、淋巴结转移、远处转移及临床分期呈正相关(P<0.01)。MVD≤28个/HP的胃癌患者总生存期较MVD>28个/HP患者明显延长(分别为63.63%及28.57%),差异有统计学意义(P<0.01)。经相关分析,VEGFR-2阳性表达率与MVD呈正相关(r=0.463,P<0.01)。结论:VEGFR-2、MVD可作为大肠癌发生侵袭转移和判断预后的指标。     

基质金属蛋白酶-9在大肠癌中的表达及其与血管生成的相关性

[目的]探讨基质金属蛋白酶-9（MMP-9）在大肠癌中的表达及其与血管生成关系的临床意义。[方法]应用免疫组化SP法检测108例大肠癌组织中MMP-9、血管内皮生长因子（VEGF）的表达以及微血管密度（MVD）。[结果]MMP-9、VEGF的表达和MVD值与肿瘤分化、淋巴结转移、Dukes分期明显相关；MMP-9、VEGF阳性表达组的MVD值显著高于阴性组；MMP-9与VEGF在大肠癌组织中表达呈正相关。[结论]MMP-9与大肠癌血管生成有关，检测MMP-9的表达可作为反映大肠癌侵袭和转移的生物学指标。     

Correlation of plasma level and immunohistochemical expression of vascular endothelial growth factor in patients with advanced colorectal cancer

BACKGROUND: Vascular endothelial growth factor (VEGF) is thought to be the most potent angiogenic factor and may contribute to the progression of various cancers. In colorectal cancer, the immunohistochemical expression of VEGF is reported to be an independent prognostic factor, and elevated plasma levels of VEGF are reported to be a prognostic marker. The purpose of this study is to evaluate whether plasma levels of VEGF correlate with its immunohistochemical expression and with microvessel density (MVD) in patients with colorectal cancer. MATERIALS AND METHODS: Thirty-one patients with advanced colorectal cancer, who underwent surgery between February 1998 and April 2000, were included in this study. We measured the preoperative plasma levels of VEGF using the ELISA kit and immunostained the resected specimens for VEGF and CD34, as a marker of MVD. We then investigated the correlation among plasma levels of VEGF, expression of VEGF and MVD, and between these three factors and several clinical features. RESULTS: The plasma levels of VEGF were significantly associated with liver metastasis, the immunohistochemical expression of VEGF was significantly associated with lymph node metastasis and TNM stage, while MVD was significantly associated with lymph node metastasis, depth of invasion and TNM stage. Among the 3 parameters for angiogenesis studied, the plasma levels of VEGF significantly correlated with its immunohistochemical expression, and immunohistochemical expression of VEGF significantly correlated with MVD. There was no significant correlation between plasma levels of VEGF and MVD. CONCLUSION: Measuring plasma levels of VEGF is a good predictor of the immunohistochemical expression of VEGF in patients with advanced colorectal cancer, and may be a better indicator for tumor VEGF levels, since plasma levels can be measured much more quickly than expression levels.     

大肠腺瘤和腺癌组织中缺氧诱导因子-1α的表达及其与VEGF、微血管密度的关系

背景与目的:缺氧诱导因子-1α(hypoxia-inducible factor 1 alpha,HIF-1α)是肿瘤细胞适应缺氧而产生的一种核转录因子,在促进肿瘤新生血管生成中起重要作用。本研究旨在探讨大肠腺瘤和腺癌组织中HIF-1α的表达及其与血管内皮生长因子(vascular endothelial growth factor,VEGF)、微血管密度(microvessel density,MVD)的关系。方法:采用原位杂交技术检测HIF-1α mRNA,应用免疫组织化学方法检测VEGF蛋白的表达,用CD34单克隆抗体标记血管内皮细胞并计数MVD。结果:大肠腺癌组织HIF-1α mRNA阳性表达率为67.8％(42/62),腺瘤组织为44.4％(8/18)。腺癌组织从Dukes’A期到Dukes’C+D期HIF-lα mRNA表达阳性率不断增加(P<0.05)。HIF-1α mRNA表达平均阳性率为:腺瘤44.4％;腺癌Dukes’A期41.2％,Dukes’B期72.2％,Dukes’C+D期81.5％。腺癌组VEGF阳性表达率高于腺瘤组(59.7％ vs 33.3％,P<0.005).HIF-1α表达与VEGF呈正相关(r_s=0.768,P<0.01),与MVD呈正相关(r_s=0.683,P<0.05)。结论:HIF-1α及其靶基因 VEGF的过度表达与肿瘤新生血管形成呈正相关,这在大肠腺瘤癌变及大肠腺癌发展过程中可能起重要作用。     

血管内皮生长因子在大肠癌中的表达及临床意义

目的研究肿瘤生长因子(VEGF)和肿瘤微血管密度(MVD)的表达水平在大肠癌中的临床意义.方法对86例手术切除的大肠癌患者的临床病理资料进行研究,并采用免疫组化方法检测VEGF蛋白和MVD在大肠癌的表达水平.结果VEGF表达阳性率为62.8%.MVD和VEGF表达的程度明显相关.VEGF的阳性表达与组织学类型及肿瘤位置无显著相关(P＞0.05),而与淋巴结转移、肝肺等远处转移及浸润深度有明显相关性(P＜0.05).结论VEGF是由肿瘤细胞所分泌的,并在大肠癌的生长和转移过程中发挥重要的作用.     

p53、血管内皮生长因子在大肠癌组织中的表达与血管生成

目的　探讨p53、血管内皮生长因子 (VEGF)在大肠癌组织中的表达及其与血管生成的关系。方法　利用免疫组化SABC法 ,对 1 0 6例大肠癌组织及 2 0例正常大肠组织中的 p53、VEGF的表达及微血管密度 (MVD)进行研究。 结果　p53、VEGF的表达与肿瘤的分化程度及Dukes分期无明显相关性 (P >0 .0 5 )。p53表达阳性或VEGF表达阳性的大肠癌组织MVD明显高于p53表达阴性 (P <0 .0 1 )或VEGF表达阴性者 (P <0 .0 1 )。p53表达阳性的大肠癌组织中VEGF的表达阳性率显著高于 p53表达阴性者 (P <0 .0 1 )。结论　p53、VEGF在大肠癌的发生和发展中起着重要作用 ,可反映大肠癌的恶性程度和进展情况并作为预后的指标 ,p53作用的发挥是通过上调VEGF的表达水平来实现的     

胃癌组织中COX-2和VEGF表达及其相关性研究

目的探讨环氧合酶2(cyclooxygenase-2,COX-2)和血管内皮生长因子(vascularendothelial growthfactor,VEGF)在人胃癌组织中表达及其相关性。方法应用免疫组织化学SABC法检测53例人胃癌组织中COX-2、VEGF和CD34的表达,并以40例正常胃粘膜标本作为对照。对CD34阳性血管进行微血管密度(microvesseldensity,MVD)计数。对COX-2和VEGF的表达采用半定量计分法判定,并结合临床资料进行统计学分析。结果53例人胃癌组织中,COX-2表达阳性者44例,阳性率为83.0%;VEGF表达阳性者45例,阳性率为84.9%。COX-2表达与VEGF表达相关显著(P<0.05)。并且,COX-2和VEGF的表达与TNM分期(P<0.05,P<0.05)、淋巴结转移(P<0.01,P<0.05)和远处转移(P<0.01,P<0.05)相关。COX-2/VEGF同高表达组中MVD值(79.5±25.8)高于COX-2/VEGF同低表达组中的MVD值(45.0±13.9),差异非常显著(P<0.01)。结论胃癌组织中COX-2与VEGF共表达,并相互协同促进肿瘤血管生成和转移。     

Positive correlation of osteopontin, cyclooxygenase-2 and vascular endothelial growth factor in gastric cancer

Osteopontin (OPN), cyclooxygenase-2 (COX-2) and vascular endothelial growth factor (VEGF) are overexpressed in various experimental models of malignancy. However, the correlation and role of the three molecules in gastric cancer is unclear. In the present study, we found that OPN, COX-2 and VEGF were overexpressed in 53 cancerous tissues with gastric cancer compared with 40 normal mucosa tissues by immunohistochemistry method. Moreover, the results indicated co-expression of OPN, COX-2, and VEGF in gastric cancer. Levels of OPN, COX-2, and VEGF were all significantly correlated with TNM stage, lymph node metastasis and distant metastasis (P < 0.05), while not related to prognosis of patients. In addition, individual levels of OPN, COX-2, and VEGF were all significantly correlated with microvessel density (MVD), valued by CD34 staining directly with r-values of 0.416, 0.400, and 0.566, respectively (P < 0.01). Both OPN and COX-2 levels showed a positive correlation with VEGF (P < 0.05). Meanwhile, expression of COX-2 is in relation to OPN (P < 0.01). Overall, survival for patients with high MVD was significantly lower than for patients with low MVD (P < 0.05). Our findings indicate that OPN, COX-2, and VEGF synergically promote angiogenesis and metastasis in gastric cancer. It may be an important and useful strategy to target these molecules for prevention and therapy of tumor.     

Elevated IL-8 levels in the drainage vein of resectable Dukes' C colorectal cancer indicate high risk for developing hepatic metastasis.

To investigate the relationship between tumor angiogenesis and hematogenous metastasis in colorectal cancer, an immunohistochemical analysis using antibody against factor VIII was carried out on archival specimens of 35 primary tumors. In addition, we also evaluated the levels of vascular endothelial growth factor (VEGF) and interleukin-8 (IL-8), by an enzyme-linked immunosorbent assay (ELISA), in tumor specimens and the serum in the drainage venous blood. The levels of VEGF showed no correlation with the microvessel density and also did not increase significantly in patients with hepatic metastasis. On the other hand, the IL-8 levels in the tumor tissue (r=0.45) and the serum IL-8 levels (r=0.49) showed a significant correlation with the microvessel density. The serum IL-8 levels in patients with Dukes' C colorectal cancer and hepatic metastasis were significantly higher than in those without hepatic metastasis (p<0.05). In addition, the serum levels of IL-8 in patients with Dukes' C cancer without hepatic metastasis and those with Dukes' A and B cancer were also closely similar. These results suggest that IL-8 is associated with the microvessel density in primary tumors and thus play an important role in the occurrence of hepatic metastasis in patients with colorectal cancer. As a result, elevated levels of IL-8 in the drainage vein are considered to be a useful predictor for developing hepatic metastasis in patients with resectable colorectal cancer.     

Expressions of nuclear factor kappaB, inducible nitric oxide synthase, and vascular endothelial growth factor in adenoid cystic carcinoma of salivary glands: correlations with the angiogenesis and clinical outcome.

OBJECTIVE: To evaluate the expressions of nuclear factor kappaB (NF-kappaB p65), inducible nitric oxide synthase enzyme (iNOS), and vascular endothelial growth factor (VEGF) in relation to angiogenesis (microvessel density, MVD) and clinical outcomes in adenoid cystic carcinoma (ACC) of salivary glands. METHODS: Immunohistochemical staining was used to quantify the protein expression levels of NF-kappaB p65, iNOS, and VEGF in 80 surgically resected ACCs and 20 normal salivary tissues. In all cases of ACCs, MVD was evaluated by counting CD34-reactive endothelial cells or endothelial cell clusters. RESULTS: The nuclear localization of NF-kappaB p65 was only detected in ACC cells. Both iNOS and VEGF staining activities in ACCs were more significant than those in normal gland tissues (P < 0.01). MVD had significant correlations with NF-kappaB p65, iNOS, and VEGF expressions (P < 0.01). In three histologic types of ACCs, the NF-kappaB, iNOS, VEGF expressions, and MVD were significantly higher in solid type than in cribriform and tubular types (P < 0.01). The NF-kappaB, iNOS, VEGF expressions, and MVD were significantly correlated with clinical stage, tumor size, vascular invasion, recurrence, and metastasis (P < 0.05). Multivariate analysis showed NF-kappaB, iNOS and VEGF expression, MVD, solid histotype, and perineural invasion had an independent prognostic effect on overall survival. CONCLUSION: The expressions of NF-kappaB p65, iNOS, and VEGF were related with MVD. Clinical outcomes raised the possibility that the overexpression of these cytokines might contribute to tumor angiogenesis and have prognostic value in ACCs.