人喉癌组织中浸润树突状细胞抗原提呈效应的形态学研究

目的:探讨人喉癌组织中肿瘤浸润树突状细胞(tumor infiltrating dendritic cell,TIDC)肿瘤抗原提呈效应。方法:采用光镜、透射电镜和免疫组化方法观察28例手术切除的人喉癌中TIDC和肿瘤浸润淋巴细胞(tumor infiltrating lymphocytes,TIL)的形态学表现。结果:早期人喉癌组织中TIDC主要分布在癌周区及癌巢内,病变早期TIDC和TIL的浸润比晚期明显(P<0．01)。透射电镜下可见形态不一的TIDC和TIL广泛分布于癌巢边缘、游走于癌周边组织的血管和淋巴管周围。TIDC与肿瘤细胞、TIDC与TIL、TIL与TIL、TIL与肿瘤细胞之间存在多种形式的膜接触。与TIL接触的肿瘤细胞,细胞核均质化。细胞膜消失呈凋亡状态。癌晚期TIDC与TIL数量明显减少,于癌巢内常见凋亡的TIDC与TIL。结论:人喉癌组织中存在不同形态的TIDC与TIL,TIDC、TIL、癌细胞彼此密切接触发生免疫应答反应,TIDC、TIL的数量和活跃状态与肿瘤进展密切相关。     

MMP-2、Fhit、RECK、VEGF在喉癌组织中的表达及相关性分析

目的:探讨基质金属蛋白酶-2(MMP-2)、脆性组氨酸三联体基因(Fhit)、逆转录诱导蛋白基因(RECK)、血管内皮细胞生长因子(VEGF)在喉癌组织中的表达及其相关性。方法:选取2011年1月到2016年12月在陕西省人民医院接受治疗的喉癌患者80例,收集其手术中切除的喉癌组织和癌旁组织,另收集40例喉癌组织切除外缘的正常喉粘膜组织。比较喉癌组织、癌旁组织、正常喉粘膜组织中MMP-2、Fhit、RECK、VEGF的表达,分析喉癌组织中MMP-2、Fhit、RECK、VEGF的表达与临床病理特征的关系,并分析四个指标的相关性。结果:喉癌组织中MMP-2、VEGF表达明显高于癌旁组织和正常喉粘膜组织,Fhit、RECK表达明显低于癌旁组织和正常喉粘膜组织(P0.05)。喉癌组织中MMP-2的表达与淋巴结转移、临床分期、分化程度有关(P0.05);Fhit、RECK的表达与淋巴结转移、临床分期有关(P0.05);VEGF的表达与淋巴结转移有关(P0.05)。喉癌组织中MMP-2的表达水平与Fhit、RECK呈负相关(P0.05),与VEGF呈正相关(P0.05);Fhit与RECK呈正相关(P0.05),与VEGF呈负相关(P0.05);RECK与VEGF呈负相关(P0.05)。结论:在喉癌组织中MMP-2、Fhit、RECK、VEGF均存在异常表达;其相互影响,可能共同参与了喉癌的发生、发展。     

抗原负载DCs诱导的CIK细胞对B16黑色素瘤抑制作用的形态学观察

目的:探讨抗原负载树突状细胞(dentritic cells,DCs)诱导的CIK(cytokine induced killer)细胞对B16黑色素瘤的抑瘤作用。方法:分离、培养DC和CIK细胞,取部分DC进行肿瘤抗原负载,将其与CIK细胞按1:10的比例共培养3d,即为抗原负载的DC-CIK。建立B16黑色素瘤小鼠模型,分别于瘤周围皮下注射经Brdu标记的CIK、DC-CIK、抗原负载DC-CIK。按注射细胞进行分组,测量注射前后各组小鼠的瘤体积,计算抑瘤率,比较其抑瘤作用。应用免疫组化方法和透射电镜观察抗原负载DC-CIK细胞在皮肤中的分布及杀伤肿瘤细胞的形态学表现。结果:抗原负载DC诱导的CIK(细胞组抑瘤率(86.57%)高于CIK细胞组(33.34%,P<0.05)和DC-CIK细胞组(61.08%,P<0.05);光镜下抗原负载DC-CIK细胞主要分布在皮下组织,癌组织周围,特别是癌巢周边。透射电镜下抗原负载DC-CIK细胞体积大,核有切迹,细胞质内细胞器丰富,粗面内质网扩张。细胞表面有突起,与肿瘤细胞密切接触。大量肿瘤细胞凋亡、坏死。结论:CIK细胞经抗原负载DC诱导后抑瘤作用明显强于单纯CIK细胞和DC-CIK细胞。     

非小细胞肺癌中DPC4、VEGF基因的表达及相关性研究

目的:研究DPC4和VEGF基因在非小细胞肺癌中的表达及相关性.方法:利用免疫组织化学SP法检测60例NSCLC组织、10例相应的癌旁正常肺组织中DPC4、VEGF的表达.结果:DPC4在60例NSCLC标本中的阳性表达率为63.3%(38/60),癌旁正常肺组织中的阳性表达率90.0%(9/10),差别有显著性意义(P＜0.05);DPCA与患者的年龄、性别、组织学类型、TNM分期、肿瘤细胞分化程度无关(P＞0.05),而与淋巴结转移显著相关(P＜0.05).肺癌组织中VEGF阳性率(81.7%,49/60)明显高于正常肺组织(20.0%,2/10),有显著性差别(P＜0.05);VEGF的阳性表达与患者的年龄、性别、组织学类型无关(P＞0.05),而与TNM分期、肿瘤细胞分化程度、淋巴结转移明显相关.60例NSCLC中,DPCA的表达与VEGF呈明显的负相关(r=0.303,P＜0.05).结论:DPC4在肺癌组织中低表达,可促进肺癌的淋巴结转移.VEGF在肺癌组织中高表达,可促进肺癌的发生、发展、转移.DPC4、VEGF在肺癌中的表达呈负相关,提示DPC4可能通过下调VEGF的表达而抑制血管的生成.     

透明质酸介导的树突状细胞肿瘤抗原提呈效应的形态学研究

目的:探讨透明质酸对树突状细胞肿瘤抗原提呈效应的调节作用.方法:建立B16黑色素瘤小鼠模型;用GM-CSF和IL-4诱导扩增小鼠骨髓来源的树突状细胞,并用透明质酸孵育,Brdu标记;经肿瘤周围皮下回输,以普通DC、生理盐水为对照组;测量瘤体积,计算抑瘤率.光镜、透射电镜、免疫组织化学法观察HA-DC于肿瘤局部组织和淋巴结内的分布和形态学特征.结果:HA-DC细胞组的抑瘤作用强于DC细胞组(P＜0.05);HA-DC细胞主要分布于肿瘤周围和淋巴结副皮质区,透射电镜观察可见HA-DC组肿瘤周围组织中有大量树突状细胞和淋巴细胞浸润,相互有膜接触,淋巴细胞以突起深入肿瘤细胞,并与其接触、融合,肿瘤细胞发生凋亡.结论:DC负载透明质酸后可以有效激活和扩增淋巴细胞,增强机体肿瘤特异性CTL效应.     

非小细胞肺癌中NF-κ B、VEGF 的表达及其与肿瘤血管形成的研究

目的:探讨核因子-κB(NF-κB)和血管内皮生长因子(VEGF)在非小细胞肺癌中的表达及其与肿瘤血管形成的关系。方法:应用免疫组织化学方法检测56例非小细胞肺癌及20例癌旁肺组织中的NF-κB P65、VEGF的表达,并用抗CD34测定肿瘤血管的密度(MVD)。结果:(1)在非小细胞肺癌中NF-κB P65、VEGF的表达阳性率分别为83.9%(47/56)、69.6%(39/56),明显高于癌旁组织(P<0.05);(2)NF-κB P65的表达在不同的TNM分期、淋巴结及胸腔积液、吸烟的分组之间差异有统计学意义,VEGF的表达在淋巴结及胸膜转移之间差异有统计学意义;(3)NF-κB P65、VEGF、MVD三者间存在明显相关性。结论:NF-κB、VEGF异常表达与NSCLC的发生、发展及肿瘤血管的形成密切的关系。     

CCR7和B7-2在抗原负载树突状细胞诱导特异性CTL抗肿瘤效应中的表达和意义

目的:研究CCR7(趋化因子受体7)和B7-2(白细胞分化抗原86)与抗原负载树突状细胞(dentritic cell,DC)诱导特异性CTL(细胞毒性T淋巴细胞)抗肿瘤效应的关系.方法:分离和培养DC,制备B16黑色素瘤细胞抗原,进行共培养,即为抗原负载的DC,建立B16黑色素瘤小鼠模型,于肿瘤周围皮下注射抗原负载的DC.应用原位杂交和免疫组织化学方法检测CCR7和B7-2的表达情况.结果:原位杂交和免疫组织化学染色显示,CCR7和B7-2阳性细胞主要分布于肿瘤周围组织,随着注射抗原负载DC时间的进展,CCR7和B7-2呈强阳性表达.结论:CCR7和B7-2的表达与抗原负载树突状细胞诱导特异性CTL抗肿瘤效应有关.     

肾细胞癌组织中PTEN和HIF-1α的表达及临床意义

目的:探讨PTEN和HIF-1α在肾细胞癌组织中的表达及临床意义。方法:随机选取2012年1月~2016年1月我院留样的90例肾细胞癌组织(肾癌组)、90例癌旁非癌组织(癌旁组),另选取30例非癌正常肾组织作为正常组,利用免疫组化法检测组织中PTEN和HIF-1α的表达,并分析其与肾细胞癌临床特征的关系。结果:PTEN主要表达在细胞浆,HIF-1α主要表达在细胞核,PTEN、HIF-1α在三组间的表达均有统计学差异(P0.05);PTEN高表达阳性率与Robson分期、Fuhmian分级、有无淋巴结转移、有无远处转移有关(P0.05),HIF-1α高表达阳性率与Robson分期、病理分型、Fuhmian分级、有无淋巴结转移、有无远处转移有关(P0.05);PTEN表达与肾细胞癌Robson分期和Fuhrman分级均呈负相关(r=-0.581,-0.442,P0.05);HIF-1α表达与肾细胞癌Robson分期和Fuhrman分级均呈正相关(r=0.597,0.489,P0.05);PTEN与HIF-1α表达呈负相关(r=-0.435,P0.05)。结论:PTEN和HIF-1α的表达与肾细胞癌的临床分期、组织学分级以及淋巴结和远处转移等具有明显关联性,可作为提示肾细胞癌的进展的指标。     

肝细胞癌和癌旁肝组织中HIF-1α和VEGF的表达及其临床意义

目的研究肝细胞癌和癌旁肝组织中HIF-1α和VEGF表达及其临床意义。方法利用免疫组织化学检测62例肝细胞癌和癌旁肝组织中HIF-1α、VEGF和CD34的表达。结果HCC中HIF-1α和VEGF的阳性率和阳性表达强度均明显高于癌旁肝组织,且两者表达强度呈显著正相关(P<0.01);癌旁肝硬化和非典型增生的肝细胞亦呈HIF-1α强表达;HIF-1α和VEGF的表达强度与HCC分化程度、肿瘤大小及MV密度呈显著正相关。结论HIF-1α在HCC发生发展过程中可能起重要作用,其表达与HCC的某些生物学行为密切相关,检测HCC组织中HIF-1α的表达有可能作为评估预后的重要指标之一。     

VEGF、P-ACC、LKB1在非小细胞肺癌组织中的表达及意义

目的:探究非小细胞肺癌组织中血管内皮生长因子(VEGF)、磷酸化乙酰辅酶A羟化酶(P-ACC)、肝激酶B1(LKB1)表达及其与肿瘤血管生成的关系。方法:将我院收治的83例非小细胞肺癌(NSCLC)患者作为研究对象,取其NSCLC病理组织样本进行研究,同时取其远离肿瘤的外周正常肺组织作为对照。采用免疫组化法测定其NSCLC病理组织样本和正常组织样本VEGF、P-ACC、LKB1的表达情况,分析比较NSCLC病理组织的VEGF、P-ACC、LKB1表达情况与其病理特征及肿瘤血管生成的关系。结果:NSCLC组织样本的VEGF阳性表达率为72.29%,明显高于癌旁正常组织样本(22.89%)(P0.05);同时,其P-ACC、LKB1阳性表达率分别为31.33%、61.45%,明显低于癌旁正常组织样本(分别为75.90%、90.36%)(P0.05)。NSCLC组织VEGF阳性表达与N分期、临床分期以及肿瘤微血管密度(MVD)有关,P-ACC阳性表达与T分期、临床分期以及MVD有关,LKB1阳性表达与N分期、临床分期、分化程度以及MVD有关(P0.05)。在样本中,VEGF阳性NSCLC组织的MVD水平明显高于VEGF阴性样本,而P-ACC、LKB1阳性NSCLC组织的MVD水平明显低于阴性样本(P0.05)。结论:非小细胞肺癌组织中VEGF在呈高表达,P-ACC、LKB1呈现低表达。VEGF、P-ACC、LKB1的表达与NSCLC临床病理特征及肿瘤血管生成均存在密切联系,对于预测NSCLC癌细胞的生长、浸润和转移具有重要意义。     

人胃癌组织中乙酰肝素酶和S-100蛋白的表达及其意义

目的:探讨乙酰肝素酶和S-100蛋白在人胃癌组织中的表达及其意义。方法:根据胃癌的病理大体分型将40例胃癌组织分为早期组和晚期组。其中,早期组同时未伴有淋巴结转移,晚期组伴有淋巴结转移。采用光镜、透射电镜、原位杂交和免疫组化方法对这两组胃癌组织的超微结构,乙酰肝素酶和S-100蛋白表达进行检测。结果:早期组乙酰肝素酶阳性表达细胞较少,晚期组阳性细胞较多,二者数密度和面密度比较。具有统计学意义(P<0.01);早期组S-100蛋白阳性表达细胞较晚期组多,二者比较,具有统计学意义(P<0.01);电镜观察可见:在胃癌早期,淋巴细胞和树突状细胞浸润较多,树突状细胞突起与淋巴细胞相接触,基底膜基本完整。晚期,基底膜几乎消失。淋巴细胞和树突状细胞浸润较少,癌细胞穿基膜明显。结论:乙酰肝素酶和S-100蛋白的表达程度可作为判定胃癌的侵袭和转移的指标,对其预后的判断具有参考价值。     

VEGF、CD34、VEGF—C和VEGFR-3在胃癌中的表达及临床意义

目的：探讨胃癌组织中VEGF、CD34、VEGF-C和VEGFR-3的表达情况及临床意义。方法：采用免疫组化方法测定81例胃癌组织VEGF、CD34、VEGF—C和VEGFR-3表达情况,并结合患者的临床病理资料进行分析。结果：81例胃癌组织中MVD平均值为（42.95±14．79）个／视野,范围为13．00-68．33个／视野,VEGF、VEGF—C、VEGFR-3阳性表达率分别为74．1％、64．2％、67．9％。VEGF的表达与肿瘤的TNM分期、浸润深度、淋巴结转移有关,CD34的表达与肿瘤的分化程度、TNM分期、浸润深度、淋巴结转移有关,VEGF—C的表达与肿瘤的分化程度、浸润深度、淋巴结转移有关,VEGFR-3的表达与肿瘤的浸润深度、淋巴结转移有关。结论：VEGF、CD34、VEGF—C和VEGFR-3的表达与胃癌的浸润转移密切相关。     

Expression and Biological Significance of Leptin,Leptin Receptor,VEGF, and CD34 in Colorectal Carcinoma

To investigate the expression and biological significance of Leptin, Leptin receptor, Vascular Endothelial Growth Factor (VEGF), and CD34 protein in colorectal carcinoma tissues. The expression of Leptin, Leptin receptor, VEGF, and CD34 was detected in 68 cases of colorectal carcinoma tissues, paired para-carcinoma tissues and normal colorectal tissues by Immunohistochemical SP Method. The results and related clinicopathological data were analyzed. The positive rate of Leptin, Leptin receptor, and VEGF was significantly higher in colorectal carcinoma tissues than that in paired para-carcinoma tissues and normal colorectal tissues. The expression of Leptin, Leptin receptor, and VEGF was correlated with grade of tumor differentiation, depth of bowel wall invasion, lymph node metastasis, Dukes stage, distant metastasis, and lympho/vascular tumor embolization. Microvessel density (MVD) value in colorectal carcinoma was significantly higher than that in para-carcinoma tissues and normal colorectal tissues, and the density in para-carcinoma tissues was higher than that in normal colorectal tissues. The expression of Leptin, Leptin receptor, VEGF, and MVD value in colorectal carcinoma was positively correlated. In conclusion, microvessel density value is an important index of the growth, invasion, and metastasis of colorectal carcinoma. The binding of Leptin and Leptin receptor promotes the proliferation of colorectal carcinoma cells. The synergy between Leptin and VEGF accelerates the angiogenesis in colorectal carcinoma and accelerates the invasion and metastasis of the tumor cells.     

CD40 is overexpressed by HPV16/18-E6 positive cervical carcinoma and correlated with clinical parameters and vascular density

CD40 is expressed in many tumor cells, however, its role in tumor biology is yet to be demonstrated. In the present study, we investigated the role of CD40 in cervical carcinoma. In vivo, we evaluated CD40 expression in 56 cervical carcinoma tissues, 43 cervicitis and 38 normal cervix, and investigated the relationship between CD40 and HPV antigen, histopathological parameters, vascular density, and vascular endothelial growth factor (VEGF) expressions. The results clearly demonstrated that CD40 expression, including membranous and cytoplasmic staining, was significantly higher in cervical carcinoma than in the cervicitis and normal cervix. The expression of CD40 was significantly correlated with HPV and VEGF expressions and microvessel density (MVD). These observations provide evidence that CD40 may be involved in neovascularization of cervical carcinoma, they also suggest that CD40 and VEGF may be useful biomarkers for evaluating the risk of developing cervical carcinoma, and may also be used as a target for therapy.     

DC‐CIK cells derived from ovarian cancer patient menstrual blood activate the TNFR1‐ASK1‐AIP1 pathway to kill autologous ovarian cancer stem cells

Ovarian cancer stem cells (OCSCs) are highly carcinogenic and have very strong resistance to traditional chemotherapeutic drugs; therefore, they are an important factor in ovarian cancer metastasis and recurrence. It has been reported that dendritic cell (DC)‐cytokine‐induced killer (CIK) cells have significant killing effects on all cancer cells across many systems including the blood, digestive, respiratory, urinary and reproductive systems. However, whether DC‐CIK cells can selectively kill OCSCs is currently unclear. In this study, we collected ovarian cancer patient menstrual blood (OCPMB) samples to acquire mononuclear cells and isolated DC‐CIK cells in vitro. In addition, autologous CD44+/CD133+ OCSCs were isolated and used as target cells. The experimental results showed that when DC‐CIK cells and OCSCs were mixed and cultured in vitro at ratios of 5:1, 10:1 and 50:1, the DC‐CIK cells killed significant amounts of OCSCs, inhibited their invasion in vitro and promoted their apoptosis. The qPCR and Western blot results showed that DC‐CIK cells stimulated high expression levels and phosphorylation of TNFR1, ASK1, AIP1 and JNK in OCSCs through the release of TNF‐α. After the endogenous TNFR1 gene was knocked out in OCSCs using the CRISPR/Cas9 technology, the killing function of DC‐CIK cells on target OCSCs was significantly attenuated. The results of the analyses of clinical samples suggested that the TNFR1 expression level was negatively correlated with ovarian cancer stage and prognosis. Therefore, we innovatively confirmed that DC‐CIK cells derived from OCPMB could secret TNF‐α to activate the expression of the TNFR1‐ASK1‐AIP1‐JNK pathway in OCSCs and kill autologous OCSCs.     

应用siRNA技术探讨MCF-7乳腺癌细胞分泌的VEGF对树突状细胞的影响

为探讨MCF-7乳腺癌细胞分泌的血管内皮生长因子（ vascular endothelial growth factor, VEGF）对树突状细胞（dendritic cell, DC）功能及其分化的影响,针对VEGF基因设计siRNA（small interfering RNA, siRNA),采用脂质体转染法以100 nmol/L最佳转染浓度导入MCF-7乳腺癌细胞（siRNA组）,以脂质体Lipofectamine　2000TM转染MCF-7 乳腺癌细胞培养上清培养正常DC作为对照（对照组）,采用ELISA法检测经siRNA 干扰VEGF基因后的MCF-7 乳腺癌细胞分泌的VEGF因子含量, Western 印迹检测VEGF蛋白表达,以探讨siRNA的基因沉默效果;以siRNA组和对照组培养上清分别培养外周血单个核细胞,用流式细胞仪检测所诱导DC表型CD1a、CD80、CD83、CD86和HLA-DR的表达,用MTT法检测转染前后两组DC 诱导的细胞毒性T淋巴细胞（cytotoxic T lymphocyte, CTL）对MCF-7细胞的细胞毒作用.结果显示,MCF-7 乳腺癌细胞培养上清能明显抑制正常DC分化成熟及抗原递呈能力,干扰VEGF基因后MCF-7 乳腺癌细胞培养上清对DC的影响明显降低,CD80、CD83、CD86和HLA-DR的表达较对照组显著升高,而CD1a表达下降（P＜0.01）.转染前后DC 诱导的CTL对MCF-7细胞的杀伤活性有明显差异（P＜0.01）.由此可见,siRNA可靶向抑制MCF-7乳腺癌细胞VEGF的表达,下调VEGF后的MCF-7 细胞上清对DC分化成熟及功能的抑制作用明显降低,从而推测VEGF在肿瘤的发生、发展和免疫抑制方面可能起着重要的作用.     

食管鳞状细胞癌中HDGF、VEGF表达与微血管形成的关系

目的:研究食管鳞状细胞癌中肝癌衍生生长因子(HDGF)、血管内皮生长因子(VEGF)的表达及其与微血管形成的关系。方法:通过免疫组化SABC法检测和比较68例食管鳞癌、20例切缘正常组织中HDGF、VEGF的表达和CD34标记的微血管密度(MVD),分析HDGF和VEGF表达之间的关系及其与食管鳞癌患者临床病理因素和食管癌组织MVD值的关系。结果:食管鳞癌组织中HDGF(63.2%)和VEGF(72.1%)的阳性表达率均明显高于切缘正常粘膜组织(15.0%、20.0%)(P0.05),食管鳞癌组织和切缘正常粘膜组织中的MVD值分别为35.48±5.75和13.50±2.1(P0.05)。食管鳞癌组织HDGF的阳性表达率仅与其临床分期明显相关(P0.05),而VEGF的阳性表达率与其淋巴结转移、临床分期均显著相关(P0.05),二者在食管鳞癌组织中的表达呈显著正相关(P0.05)。食管鳞癌组织中HDGF、VEGF阳性表达组MVD值均明显高于HDGF、VEGF阴性表达组(P0.05)。结论:HDGF可能通过诱导VEGF的产生,从而促进血管生成,参与食管鳞癌的发生、发展及转移。     

Abnormally enhanced blood concentrations of vascular endothelial growth factor (VEGF) in metastatic cancer patients and their relation to circulating dendritic cells, IL-12 and endothelin-1

Elevated VEGF blood concentrations have been proven to be associated with poor prognosis in human neoplasms. This finding is generally explained as a consequence of the potential angiogenic properties of VEGF itself. However, preliminary experimental studies suggest that VEGF, in addition to its angiogenic activity, may also play an immunosuppressant role by inhibiting dendritic cell (DC) maturation. The present study was performed to analyze blood levels of VEGF in cancer patients in relation to those of another potentially angiogenic tumor growth factor, endothelin-1 (ET-1), and to the absolute number of circulating immature and mature DC, and serum levels of the best known antitumor cytokine, IL-12. The study was performed in 100 healthy controls and in 80 solid tumor patients (colorectal cancer: 24; gastric cancer: 17; cancer of pancreas: 4; lung cancer: 13; breast cancer: 11; renal cell cancer: 6; gynecologic tumors: 5), 48 of whom showed distant organ metastases. In each patient, we have evaluated serum concentrations of VEGF-165, total VEGF, ET-1, IL-12 and the circulating number of immature (CD123+) and mature (CD11c+) DC. Mean serum levels of VEGF-165 were significantly higher in metastatic patients than in controls or in non-metastatic patients, whereas the total amounts of VEGF were not significantly higher. Moreover, it has been observed that patients with abnormally elevated blood concentrations of VEGF-165 showed significantly lower mean values of immature DC, mature DC and IL-12 and significantly higher mean levels of ET-1 than those with normal concentrations. This study, by confirming that advanced neoplastic disease may be associated with increased endogenous secretion of VEGF, seems to suggest that the association between high blood levels of VEGF and poor prognosis in cancer does not depend only on VEGF-induced stimulation of the neovascularization, but also on VEGF-related immunosuppression.     

Surrogate markers of tumoral angiogenesis

BACKGROUND: Angiogenesis is a prerequisite for tumor growth and metastasis. Vascular cell adhesion molecule1 (VCAM-1) is expressed on endothelial cells as a result of vascular endothelial growth factor (VEGF) stimulation. PURPOSE: To determine if measurement in serum of VEGF or VCAM-1 provides an accurate measure of tumor angiogenesis. METHODS: VCAM-1 and VEGF were measured in the serum of women with early and advanced breast cancer by ELISA. Levels were compared to levels of VCAM-1 and VEGF in women with normal breasts and levels of the endothelial glycoprotein von Willebrand factor. Levels of VEGF and VCAM-1 in women with early breast cancer were correlated with established clinicopathological prognostic markers and intratumoral microvessel density (IMD). RESULTS: In early breast cancer serum VCAM-1 correlated closely with the microvessel density in tumors (r=0.61, p<0.001). Women with lymph node-positive and high-grade tumors had higher levels of serum VCAM-1 than women with lymph node-negative and low-grade tumors. Serum VEGF demonstrated no correlation with established prognostic features or IMD. Levels of VCAM-1 and VEGF were raised in women with advanced breast cancer. CONCLUSION: Serum VCAM-1 is a surrogate marker of angiogenesis in breast cancer and its measurement may help in the assessment of antiangiogenic drugs currently in phase II trials.