乳腺癌血管内皮生长因子与微血管密度的分布及与预后的关系

[目的]观察乳腺癌中血管内皮细胞生长因子 (vascularendothelialgrowthfactor,VEGF)的表达和微血管密度 (microvesseldensity,MVD)的分布 ,并探讨VEGF和MVD与预后的关系。[方法]用Ⅷ因子抗体与抗VEGF多克隆抗体分别作病理切片的免疫组织化学染色 ,在显微镜下判断VEGF染色程度和进行微血管计数。[结果]乳腺癌的VEGF表达阳性率为51.35% (38/74) ,MVD均值为(30.8±19.4)个 /200倍视野。VEGF和MVD均与腋淋巴转移及复发转移有关(P<0.05) ,与无瘤生存率明显相关。[结论]VEGF与MVD与患者的预后相关 ,均可作为判断乳腺癌患者预后的指标之一。     

乳腺癌血管内皮生长因子与微血管密度的免疫组织化学研究

 血管内皮生长因子（VEGF）是特异作用于血管内皮细胞、上调血管生成的重要因子，能刺激血管内皮细胞增殖、迁徙和诱导血管生成，而血管新生是实体瘤生长、浸润、转移与复发的重要前提。本实验采用免疫组织化学SP法对48例乳腺癌组织中VEGF表达、MVD与乳腺癌生物学行为间的关系进行探讨。     

血管内皮生长因子及微血管密度在乳腺癌中的表达及意义

目的 研究血管内皮生长因子(VEGF)及微血管密度(MVD)在乳腺癌组织中的表达及意义。方法 应用免疫组化SP法检测81例原发性乳腺癌患者癌组织MVD和VEGF的表达。结果 VEGF高表达者49例(60．5％)，MVD计数高者35例(43．2％)。VEGF、MVD与肿瘤TNM分期有关，但与年龄、肿瘤大小、雌激素受体(ER)表达及淋巴结状况无关；VEGF与MVD的表达有显著相关性。单因素预后分析显示，MVD及VEGF低表达者无病生存期(DFS)及总生存期(OS)长于高表达者。分组的单因素分析表明，VEGF与各组患者的DFS有显著相关性，与淋巴结( )和Ⅲ期乳腺癌患者的OS有显著相关性；而MVD与淋巴结( )患者的DFS和OS以及Ⅲ期乳癌患者的DFS有显著相关性。多元回归分析显示，MVD是风险因子，表达越高生存期越短。结论 VEGF和MVD均为判断乳腺癌须后的有效指标，其中MVD可能是预测乳腺癌预后的独立因子。     

人脑胶质瘤中微血管密度和血管内皮生长因子表达的意义

血管生成对肿瘤的生长至关重要,抑制血管生成是不同于常规的新的抗肿瘤策略,在一些肿瘤实验性治疗中已取得理想疗效[1～3]。血管内皮生长因子(vascularendothelialgrowthfactor,VEGF)是一种强烈的促血管生成因子,在乳腺癌、胃癌、前列腺癌、黑色素瘤等中VEGF与微血管密度(microvesseldensity,MVD)密切相关[4]。为探讨胶质瘤中VEGF表达及血管生成的临床病理意义,我们应用免疫组化技术进行了研究。 1　资料与方法 1.1　临床资料 　　67例人脑胶质瘤标本选自1998年3月～2000年3月手术切除并经病理证实的胶质瘤患者,其中男37例,女30例,年龄12～69岁,中位年龄38岁。按1993年WHO中枢神经系统肿瘤分类法[5],本组病人低恶性度（星形细胞瘤Ⅰ～Ⅱ级）23例,中恶性度(间变性胶质瘤)22例,高恶性度（多形性胶质母细胞瘤）22例。8例正常脑组织系颅内减压手术中获得。各标本切取后常规石蜡包埋,作5μm连续切片,1张作HE染色用于重新确认病理结果,其余切片作免疫组化染色。     

血管内皮生长因子和微血管密度在食管癌中的临床意义

目的:探讨VEGF表达和MVD与食管癌临床病理指标和预后的相关关系.方法:用免疫纽化法检测43例食管癌VEGF蛋白表达和MVD,应用等级相关检验研究VEGF和MVD与食管癌临床病理指标、局控率、总体生存率及无瘤生存率的相关关系.结果:VEGF表达与食管癌T分期呈正相关;MVD与病灶部位、组织学分化相关.多因素分析显示切缘阳性是影响局控率的预后因素;病灶部位、切缘阳性、T分期和VEGF表达是影响总体生存率和无瘤生存率的预后因素;MVD与预后无显著相关.结论:VEGF可能反映食管癌病变进展情况,并有助于预后判断,值得今后扩大样本量进一步研究.     

血管内皮生长因子表达及微血管密度与放射敏感性

血管内皮生长因子(VEGF)是一种具有肝素结合活性的生长由子，能特异作用于血管内皮细胞，对血管生长有板强R诱导作用。VEGF的表达与肿瘤内微血管密度(MVD)呈明显正相关。缺氧是VEGF表达最主要的调节因素。恶性肿瘤在生长过程中，由于组织增生过快必然会造成局部组织缺氧，从而诱导VEGF表达；而乏氧细胞对射线抗拒。所以，有希望以VEGF的表达及MVD来预测放射敏感性。     

宫颈癌患者血管内皮生长因子和微血管密度表达与侵袭转移的关系

目的探讨宫颈癌患者血管内皮生长因子(VEGF)及其微血管密度(MVD)的表达与肿瘤侵袭转移的关系。方法采用免疫组织化学方法检测52例慢性宫颈炎组织及60例宫颈癌组织VEGF及MVD的表达情况。结果宫颈癌组织及慢性宫颈炎组织VEGF阳性率分别为61.7%和7.7%,差别具有统计学意义(P<0.05);宫颈癌组织MVD计数显著高于慢性宫颈炎组织(45.38±10.28 VS 5.10±1.12,P<0.05);VEGF及MVD表达与肿瘤淋巴转移、临床分期及分化程度显著相关(P<0.05),而与年龄、病理分型无相关性(P>0.05)。结论宫颈癌组织VEGF及MVD表达显著升高,且与肿瘤的侵袭性密切相关,二者高表达患者预后不良。     

血管内皮生长因子及微血管密度在肝癌中的表达

目的 :探讨血管内皮生长因子 (VEGF)在肝癌微血管形成中的作用以及与原发性肝癌生物学行为的关系。方法 :选择 32例原发性肝癌手术标本 ,采用免疫组织化学方法测定血管内皮生长因子及Ⅷ因子的蛋白表达。结果 :血管内皮生长因子在原发性肝癌中的阳性表达率为 6 5 .6 3% ;原发性肝癌中肿瘤微血管密度 (MVD)为 30 .96± 12 .32 ,其中血管内皮生长因子表达阴性者MVD为 19.12± 7.34 ,血管内皮生长因子表达阳性者MVD为 42 .36±15 .5 4,二者相比有显著差异 (P <0 .0 1)。结论 :血管内皮生长因子能促进肿瘤中微血管形成 ,血管形成在原发性肝癌的生长和转移中起到重要的作用。     

微血管密度和血管内皮生长因子与大肠癌肝转移的关系研究

目的研究微血管密度(MVD)和血管内皮生长因子(VEGF)与大肠癌术后发生肝转移的关系。方法检测160例大肠癌标本中VEGF、和MVD的表达并结合随访结果。结果 VEGF、和MVD与大肠癌的临床分期密切相关:Duke C期的vEGF和MVD表达高于B期,差异有显著性(p<0.01);术后发生肝转移组VEGF和MVD表达高于无转移组,差异有显著性(P<0.01)。结论检测大肠癌病灶中MVD和VEGF的表达能预测患者的临床分期,MVD和VEGF过度表达的患者,术后发生肝转移的危险性大。     

血管内皮生长因子表达及微血管密度与放射敏感性

血管内皮生长因子(VEGF)是一种具有肝素结合活性的生长因子,能特异作用于血管内皮细胞,对血管生长有极强R诱导作用.VEGF的表达与肿瘤内微血管密度(MVD)呈明显正相关.缺氧是VEGF表达最主要的调节因素.恶性肿瘤在生长过程中,由于组织增生过快必然会造成局部组织缺氧,从而诱导VEGF表达;而乏氧细胞对射线抗拒.所以,有希望以VEGF的表达及MVD来预测放射敏感性.     

乳腺癌组织中PSA mRNA和VEGF mRNA的表达及其关系

目的探讨前列腺特异抗原(PSA)mRNA和血管内皮细胞生长因子(VEGF)mRNA在乳腺癌组织中的表达及其关系。方法采用半定量逆转录聚合酶链式反应(RT-PCR)检测35例乳腺癌、12例癌旁乳腺组织和10例乳腺纤维腺瘤组织中的表达,免疫组化检测35例乳腺癌组织中ER、PR的表达,分析PSA mRNA和VEGFmRNA表达之间的关系。结果PSA mRNA在乳腺癌组织中的表达水平明显低于癌旁乳腺组织和乳腺纤维腺瘤组织,差异有显著性(P值均=0.00)。VEGF 121、165mRNA在乳腺癌中的表达水平明显高于癌旁乳腺组织和乳腺纤维腺瘤组织的表达(P值均=0.00)。ER、PR阳性表达的乳腺癌组织中PSA mRNA表达高于ER、PR阴性者,差异有显著性(P=0.001和0.004)。PSA mRNA表达阳性者VEGF 121、165mRNA表达水平明显低于PSA mRNA表达阴性者(P=0.034、0.026)。结论PSA mRNA在乳腺癌组织中的表达下调,但其表达受ER、PR的调控,而且其可能具有抑制乳腺肿瘤血管生成的作用。     

胃癌组织中血管内皮生长因子C与肿瘤浸润性树突状细胞的相关性

目的: 探讨胃癌组织中血管内皮细胞生长因子C(vascular endothelial growth factorc, VEGFC)与肿瘤浸润性树突状细胞( tumor infiltrating dendritic cells，TIDC)在胃癌浸润转移中的作用及两者的关系。方法：52例胃癌石蜡标本选自重庆医科大学附属第一医院外科2004年9月至     

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。     

腋淋巴结阴性乳腺癌血管生成与预后相关性研究

】 ObjectiveTo determine the relation of microvessel density (MVD) and the expression of vascular endothelial growth factor (VEGF) with the prognosis of axillary-node-negative breast carcinoma (ANNBC) for searching for new prognostic factors. MethodsEighty specimens resected from patients with ANNBC were investigated by staining with a monoclonal antibody against FVⅢ-RA and polyclonal antibody against VEGF. Correlations between the expression of VEGF,MVD and several of clinicopathologic factors were studied. ResultsThe mean of MVD was 35.99± 20.27 in all patients.The positive rate of VEGF was 36.25％ . Both of them were not correlated with the clinicopathological factors. MVD was significantly higher in VEGF-positive tumors or relapsed or metastatic group than in VEGF-negative tumors or disease-free survival group. Moreover, patients with higher MVD or VEGF positive tumors had lower disease-free survival (DFS) or overall survival (OS) than those with lower MVD or VEGF-negative tumors. When those (45 cases) without adjuvant therapies after surgery were analyzed, the results were the same.But OS of them (35 cases) with adjuvant therapies had no significiant difference between high and low MVD group,and between VEGF positive and negative group. DFS was the same among VEGF positive and negative group. Multivariate analysis indicated that MVD,the expression of VEGF and tumor size were independent prognostic factors in patients with ANNBC. ConclusionsMVD,the expression of VEGF may be good prognostic indicators for patients with ANNBC and adjuvant therapies after surgery or antiangiogenic therapy may be useful to improve the prognosis of patients with high MVD or VEGF-positive tumors.     

胃癌组织中环氧化酶-2的表达与微血管密度和VEGF的关系

目的 :探讨环氧化酶 -2 (COX 2 )在胃癌组织中的表达及其与微血管密度(microvesseldensity ,MVD)和血管内皮生长因子 (vascularendothelial growthfactor ,VEGF)的关系。方法 :采用免疫组织化学法 ,检测 43例胃癌患者手术切除标本中COX 2和VEGF的表达 ,并计数MVD。结果 :COX 2在胃癌组织的阳性表达率为60 5 % ,明显高于对照组 ,P <0 0 1;并且与胃癌淋巴结的转移和临床分期有关 ,与肿瘤大小、浸润深度、分化程度均无关。COX 2和VEGF表达一致符合率为 5 3 5 % ,两者表达有显著相关性 ,P <0 0 1。COX 2阳性和VEGF阳性组MVD值 (2 2 0 8± 3 69、2 2 12± 3 5 0 )均高于COX 2阴性和VEGF阴性组 (17 68± 3 5 0、16 15± 3 2 3 ) ,P <0 0 5 ;COX 2和VEGF均为阳性者的MVD值最高 (2 2 86± 3 40 ) ,P <0 .0 5。结论 :COX 2、VEGF的表达以及MVD的测定可作为判断胃癌恶性潜能的重要生物指标。COX 2、VEGF的表达对肿瘤血管形成可能起重要作用 ,联合检测COX 2、VEGF的表达对了解肿瘤血管形成的机制有一定的作用     

Tumor microvessel density and prognosis in node-negative breast cancer

Microvessel density (MVD) of breast cancer is widely regarded as a prognostic factor, but results from studies on the most important case series have produced conflicting results. The present study was performed with confirmatory intent to define the prognostic relevance of MVD on a series of 378 node-negative-breast-cancer patients, much larger than any other series previously analyzed. Microvessels were stained using Factor-VIII antibody and an immunoperoxidase reaction. MVD was determined independently by 2 observers according to Weidner's methods. In parallel, cell proliferation was evaluated as S-phase fraction and determined according to the 3H-thymidine-labeling index method (TLI). Estrogen and progesterone receptors were quantitatively assessed using the dextran-charcoal technique. Tumor MVD varied greatly from tumor to tumor (2 to 232 MV/mm2) and was unrelated to patient age and menopausal status, or to tumor size, histology and steroid-receptor status. A significant (p = 0.004) but weak inverse correlation (rs = -0.188) was observed with cell proliferation. Univariate analysis using 40 MV/mm2 as cut-off showed an inverse relation with 5-year relapse-free survival (82% vs. 71%, p = 0.018). This finding was limited to very small tumors, slowly proliferating tumors and ER-negative tumors. Multivariate analysis identified tumor size and TLI, but not MVD, menopausal status or ER as independent prognostic factors.     

Nitric oxide in breast cancer: induction of vascular endothelial growth factor-C and correlation with metastasis and poor prognosis.

PURPOSE: Metastasis to regional lymph nodes through the lymphatic vessels is a common step in the progression of cancer. Recent evidence suggests that tumor production of vascular endothelial growth factor-C (VEGF-C) promotes lymphagiogenesis, which in turn promotes lymphatic metastasis. Nitric oxide (NO) may also increase metastatic ability in human cancers. EXPERIMENTAL DESIGN: Nitrite/nitrate levels and VEGF-C production were assessed in MDA-MB-231 breast cancer cells after induction and/or inhibition of NO synthesis. Formation of nitrotyrosine, a biomarker for peroxynitrate formation from NO in vivo, was analyzed in primary human breast carcinoma with long-term follow-up. The relationship between nitrotyrosine levels and lymph node status, VEGF-C immunoreactivity, and other established clinicopathologic variables, as well as prognosis, was analyzed. RESULTS: Production of nitrite/nitrate and VEGF-C in MDA-MB-231 cells was increased by treatment with the NO donor DETA NONOate. The NO synthase inhibitor N(G)-nitro-l-arginine methyl ester eliminated this increase. High-grade nitrotyrosine staining was observed in 57.5% (65 of 113) of the invasive breast carcinomas. Nitrotyrosine levels were significantly correlated with VEGF-C immunoreactivity and lymph node metastasis. Survival curves determined by the Kaplan-Meier method showed that high nitrotyrosine levels were associated with reduced disease-free and overall survival. In multivariate analysis, high nitrotyrosine levels emerged as a significant independent predictor for overall survival. CONCLUSIONS: Our data showed a role for NO in stimulating VEGF-C expression in vitro. Formation of its biomarker nitrotyrosine was also correlated with VEGF-C expression and lymph node metastasis. Furthermore, high nitrotyrosine levels may serve as a significant prognostic factor for long-term survival in breast cancer.     

非小细胞肺癌组织中血管内皮生长因子的表达与微血管密度的关系

 目的　探讨非小细胞肺癌 (NSCLC)组织中血管内皮生长因子 (VEGF)表达和微血管密度(MVD)的关系。方法　采用免疫组化S P法对 76例NSCLC标本中VEGF表达和MVD进行了检测。结果　在NSCLC中鳞癌的VEGF表达阳性率显著高于腺癌 (P <0 .0 5 ) ;VEGF表达阳性率和MVD值与肿瘤组织学分化程度有关 ,低分化癌VEGF表达阳性率和MVD值显著高于中、高分化癌 (P <0 .0 5 ) ;淋巴结转移阳性组NSCLC的VEGF表达阳性率和MVD值显著高于阴性组 (P <0 .0 5 )。结论　VEGF可引起瘤内MVD增多 ,促进肿瘤的生长和转移 ;检测VEGF表达强度 ,可作为判定NSCLC转移潜能和评价预后的指标