瘦素 瘦素受体VEGF和CD34在结直肠癌中的表达

目的:探讨瘦素(Leptin)、瘦素受体(Oh-R)、血管内皮生长因子(VEGF)和CD34蛋白(标记组织微血管密度以反映血管形成活跃程度的特异性抗体)在结直肠癌中的表达及其生物学意义.方法:应用免疫组化SP法检测68例结直肠癌患者的结直肠癌组织、癌旁组织和正常结直肠组织中瘦素、瘦素受体、VEGF和CD34的表达情况,结合临床病理资料进行分析.结果:瘦素、瘦素受体和VEGF在结直肠癌组织中的阳性表达率明显高于癌旁组织和正常结直肠组织,其表达与肿瘤的病理学分级、肠壁浸润深度、淋巴结转移、Dukes分期、远处转移及有脉管瘤栓明显相关.微血管密度(MVD值)在结直肠癌组织中的表达明显高于癌旁组织和正常结直肠组织,癌旁组织高于正常组织.在结直肠癌组织中瘦素、瘦素受体、VEGF的表达与CD34表达具有一致性.结论:微血管密度是衡量结直肠癌发展、浸润及转移的重要指标.瘦素与瘦素受体结合促进结直肠癌细胞增殖.瘦素与VEGF协同作用可促进结直肠癌新生血管形成,促进结直肠癌的浸润和转移.     

结直肠癌组织Survivin和VEGF表达与临床病理特征相关性的研究

目的:探讨结直肠癌组织中凋亡抑制基因Survivin和血管内皮生长因子(vascular endothelial growth factor,VEGF)表达与结直肠癌临床病理特征的相关性,及其在结直肠癌发生发展中的作用。方法:应用免疫组织化学方法检测61例结直肠癌及肿瘤切端非癌组织中VEGF及Survivin的表达。结果:Survivin在正常结直肠组织不表达,结直肠癌组织中45例(73.77%)阳性表达,VEGF在非癌结直肠组织不表达,癌组织中42例(68.85%)阳性表达。结直肠癌组织中Survivin及VEGF表达与肿瘤浸润深度、Duke分期及有无淋巴结转移关系密切,P<0.05。结论:Survivin和VEGF参与结直肠癌血管新生的调节,与肿瘤的发生发展及预后有密切关系。     

CD105和VEGF、TGF-β1在结直肠癌的表达及其与浸润、转移和血管生成的关系

目的 探讨结直肠癌中CD105和VEGF、TGF-β1的表达及与血管生成的关系.方法 应用免疫组化方法检测60例结直肠癌中CD105标记的微血管密度(MVD)和VEGF、TGF-β1的表达.结果 60例结直肠癌中CD105表达的MVD为36.50±9.43.VEGF、TGF-β1表达的阳性率为68.3%,75.0%.MVD和VEGF、TGF-β1表达与肿瘤浸润深度、淋巴结转移和Dukes分期密切相关(P＜0.05).VEGF、TGF-β1表达均与MVD呈正相关(P＜0.01),TGF-β1与VEGF也呈正相关(P＜0.05).结论 CD105、VEGF、TGF-β1关系密切,三者联合检测可作为结直肠癌新生血管和浸润转移的有价值的标志物.     

CD105在结直肠癌中的表达及其临床病理意义

目的探讨CD105在结直肠癌中的表达及其作为肿瘤新生血管标记物的临床病理意义。方法应用免疫组织化学S-P法,检测65例结直肠癌手术切除标本中CD105单克隆抗体表达的微血管密度(MVD)及其与临床病理参素之间的关系。结果CD105在结直肠癌中表达的新生血管大多局限于肿瘤实质边缘,而在正常组织的血管无表达。CD105检测的MVD为35.80±8.88,MVD值与肿瘤浸润深度、淋巴结转移和Dukes分期密切相关,有非常显著性差异(P<0.01)。结论CD105表达的MVD值可以被认为是与肿瘤浸润、转移有关的1项重要指征。     

Survivin、MMP-2、nm23-H1、VEGF及其受体Flt-1在结直肠癌中的表达及临床意义

背景与目的:近年来的研究表明,多种生物学指标与结直肠癌发生、发展以及手术后的复发转移、预后有关.本研究旨在探讨人结直肠癌组织中Survivin、MMP-2、nm23-H1、VEGF及其受体Flt-1的表达与各临床病理参数及预后的关系及临床意义.方法:采用免疫组织化学SP法,检测72例结直肠癌组织及其对照癌旁正常黏膜组织中Survivin、MMP-2、nm23-H1、VEGF及其受体Flt-1表达的状况,分析其与临床病理参数及复发转移的关系.结果:在结直肠癌中Survivin、MMP-2、nm23-H1、VEGF及其受体Flt-1的表达率分别为62.5%(45/72)、66.7%(48/72)、55.5%(40/72)、61.1%(44/72)、79.2%(57/72),均显著高于对照癌旁正常黏膜组织(P<0.01).Survivin表达与浸润深度、淋巴结转移、TNM分期及术后复发转移有关;MMP-2表达与淋巴结转移、TNM分期、术后复发转移有关;nm23-H1表达与淋巴结转移、TNM分期相关;VEGF表达与浸润深度、TNM分期及术后复发转移有关;而受体Flt-1表达与临床病理及预后因素均无关.结论:Survivin、MMP-2、nm23-H1、VEGF与结直肠癌的发生、发展密切相关,联合检测多个相关基因的表达能更准确地判断结直肠癌的生物学特征及预后判断.     

结直肠癌EGFR、VEGF、HER-2的表达特点及其临床意义

目的：探讨表皮生长因子受体（EGFR）、血管内皮生长因子（VEGF）和人类表皮生长因子受体-2（HER-2）在结直肠癌中的表达特点及其临床意义。方法：随机选取2008年6月至2011年11月在东南大学附属中大医院普外科行根治性手术的结直肠癌患者109例。应用免疫组织化学法检测结直肠癌肿瘤组织中EGFR、VEGF和HER-2的表达,并结合其临床病理特点进行统计学分析。结果：在结直肠癌组织中,VEGF蛋白的表达水平与TNM分期、有无浆膜浸润、有无淋巴结转移和远处转移具有相关性（P〈0．05）。HER-2蛋白的表达水平与有无淋巴结转移具有相关性（P〈0．05）。EGFR与VEGF蛋白表达之间具有相关性（r=0．264,P〈0．05）。结论：HER-2、VEGF参与结直肠癌的侵袭和转移过程。EGFR与VEGF在结直肠癌肿瘤组织中表达具有相关性。     

CD105和VEGF、TGF-B1在结直肠癌的表达及其与浸润、转移和血管生成的关系

目的探讨结直肠癌中CD 105和VEGF、TGF-β1的表达及与血管生成的关系。方法应用免疫组化方法检测60例结直肠癌中CD 105标记的微血管密度(M VD)和VEGF、TGF-β1的表达。结果60例结直肠癌中CD 105表达的M VD为36.50±9.43。VEGF、TGF-β1表达的阳性率为68.3%,75.0%。M VD和VEGF、TGF-β1表达与肿瘤浸润深度、淋巴结转移和Dukes分期密切相关(P<0.05)。VEGF、TGF-β1表达均与M VD呈正相关(P<0.01),TGF-β1与VEGF也呈正相关(P<0.05)。结论CD 105、VEGF、TGF-β1关系密切,三者联合检测可作为结直肠癌新生血管和浸润转移的有价值的标志物。     

VEGF和MVD在大肠癌组织中的表达及其临床意义

肿瘤的生长和转移依赖肿瘤血管的形成,血管内皮生长因子(Vascularendothelial growth factor,VEGF)在肿瘤血管形成过程中发挥重要作用[1].本研究采用免疫组织化学方法,对57例大肠癌组织标本中VEGF的表达水平及肿瘤血管密度(MVD)进行检测,探讨了VEGF在结直肠癌血管形成过程中的作用,及其与大肠癌患者预后的关系.     

结直肠癌中CD133的表达与血管生成相关性的研究

目的:研究结直肠癌组织中肿瘤干细胞标记物CD133的表达与临床病理特征之间的关系,并探讨CD133表达与肿瘤微血管密度(microvessel density, MVD)及血管内皮生长因子(vascular endothelial growth factor, VEGF)表达之间的相关性.方法:采用免疫组织化学法和组织芯片技术检测94例结直肠癌标本中CD133、VEGF和CD31的表达.结果: CD133的表达与组织分化程度(P<0.01)密切相关,而与淋巴结转移接近存在相关性(P=0.05);与VEGF表达及MVD均呈负相关(P<0.01).MVD按CD133(-)/VEGF(-/+)→CD133(+)/VEGF(-/+) →CD133(+)/VEGF(++/+++) →CD133(-)/VEGF(++/+++)的顺序逐渐增加,后两者与前两者比较,差异有统计学意义(P<0.05).结论:结直肠癌组织中癌干细胞与肿瘤MVD相关,提示前者可能通过VEGF的间接表达促进血管新生,后者密度增加则促进前者的分化成熟.     

血管内皮生长因子及其受体在结直肠癌中的表达及其意义

目的：探讨血管内皮生长因子（ＶＥＧＦ）及其受体（ＦＬＴ、ＦＬＫ－１）在结直肠癌组织中的表达及其对肿瘤新生血管生成及转移的影响。方法应用免疫组化技术,检测５０例人结直肠癌组织ＶＥＧＦ、ＦＬＴ、ＦＬＫ－１的表达和微血管密度（ｍｉｃｒｏｖｅｓｓｅｌｓ ｄｅｎｓｉｔｙ,ＭＶＤ）,并分析其与病理分型、分级、浸润深度、淋巴结、淋巴管和血管转移的相关。结果ＶＥＧＦ、ＦＬＴ、ＦＬＫ－１主要表达于癌浸润边缘和坏死组     

青年和绝经女性乳腺癌VEGF、bFGF及其受体表达的差异

目的 探讨青年和绝经女性乳腺癌血管内皮生长因子(VEGF)及其受体(FLK-1)和碱性成纤维细胞生长因子(bFGF)及其受体(HLG)的表达特征和差异。方法 以SABC免疫组化法检测40例年龄≤35岁的青年女性(青年组)和30例绝经女性(绝经组)乳腺癌组织中VEGF、FLK-1、bFGF和FLG的阳性系数值并进行比较,探讨其与腋窝淋巴结转移和临床病理特征之间的关系,同时比较两组之间各项临床指标的差异。结果 青年组腋窝淋巴结转移率和VEGF、bFGF阳性系数值明显高于绝经组,差异有显著性或极显著性(P＜0．05或P＜0．01);腋窝淋巴结转移组的VEGF、bFGF、FLK—1和FLG阳性系数值明显高于腋窝淋巴结未转移组,差异有显著性或极显著性(P＜0．05或P＜0．01);VEGF、FLK—1和FLG阳性系数值在两组的TNM临床分期0-Ⅱ期和Ⅲ-Ⅳ期组问差异有显著性或极显著性(P＜0．05或P＜0．01)。结论 青年乳腺癌侵袭性强与肿瘤血管生成相关,主要表现为VEGF和bFGF高表达。     

Vascular endothelial growth factor, FLT-1, and FLK-1 analysis in a pancreatic cancer tissue microarray

BACKGROUND: Measures of vascular endothelial growth factor (VEGF) expression in pancreatic cancer typically have been qualitative or semiquantitative. The objective of this study was to use a series of algorithms called AQUA that quantitatively assesses protein expression on tissue microarrays (TMAs) to compare in situ expression of VEGF and its primary receptors, VEGF receptor 1 (FLT-1) and VEGF receptor 1 (FLK-1), on a pancreatic cancer TMA. METHODS: TMAs were constructed by arraying 1.5-mm cores from 76 samples of pancreatic adenocarcinoma (1996-2002) that were obtained from the archives of the Yale Department of Pathology. The staining for AQUA was similar to standard immunohistochemistry and involved antigen retrieval and the application of primary antibodies, but with epifluorescence detection. Slides were counterstained with 4',6-diamidino-2-phenylindole for nuclear visualization and cytokeratin for membrane visualization. The primary antibodies used were VEGF, FLT-1, FLK-1, and cytokeratin. RESULTS: Disease stage was highly prognostic for outcome, as expected. Total amounts of VEGF and its receptors were assessed within the tumor mask and were divided into quartiles. Kaplan-Meier survival curves showed that VEGF and FLK-1 were not associated clearly with outcome. However, the expression of FLT-1 was correlated significantly, and the patients who had tumors with the lowest expression FLT-1 levels had the worst survival (P = .0038). In multivariate analysis, FLT-1 expression was an independent prognostic factor for overall survival (P = .0044). CONCLUSIONS: VEGF and its 2 principal receptors were expressed to varying degrees in tumors of the pancreas. A significant association was found between low expression of FLT-1 and both poor prognosis and advanced stage, suggesting that tumor expression of this VEGF receptor is a marker of less aggressive disease.     

Involvement of vascular endothelial growth factor and urokinase-type plasminogen activator receptor in microvessel invasion in human colorectal cancers

To evaluate the association among known angiogenic growth factors or factors related to the plasminogen activation system and clinicopathological factors in patients with colorectal cancer, we examined the expression of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), transforming growth factor-α (TGF-α), urokinase-type plasminogen activator (u-PA), u-PA receptor (u-PA-R) and plasminogen activator inhibitor-1 (PAI-1) in clinical specimens of colorectal cancers by Northern blot analysis. In comparison with the expression of these angiogenesis-related genes in 7 paired samples of colorectal cancers and the adjacent normal mucosa, VEGF mRNA level was significantly higher in the cancer tissues than in the adjacent normal mucosa (p < 0.05). We analyzed expression of these genes in 44 cases of primary colorectal cancers. Among the 3 angiogenic growth factors we examined, VEGF mRNA expression was significantly higher in the cancer tissues with blood vessel invasion or with lymphatic vessel invasion than in those without, respectively (p < 0.05). On the other hand, u-PA-R mRNA expression was significantly higher in the cancers with blood vessel invasion than in those without (p < 0.05). In addition, there was a correlation between the expression levels of VEGF and u-PA-R mRNA in the cancer tissues we have examined. Using immunohistochemistry, strong staining of VEGF or u-PA-R was observed in the cancer cells invading the microvessels. Our findings suggest that malignant transformation might accompany the upregulation of VEGF expression in colorectal cancers and that VEGF and u-PA-R might contribute cooperatively to increase angiogenesis around the tumor as well as the metastasis via microvessels. Int. J. Cancer (Pred. Oncol.) 79:179–186, 1998.© 1998 Wiley-Liss, Inc.     

Endocrine gland-derived vascular endothelial growth factor (EG-VEGF) expression in colorectal cancer

BACKGROUND AND OBJECTIVES: Vascular endothelial growth factor (VEGF) is known as an important factor in the growth and metastasis of cancer cells. In 2001, a novel angiogenesis factor, endocrine gland-derived vascular endothelial growth factor (EG-VEGF), was cloned. In this study, we investigated the expression of EG-VEGF in colorectal cancer, the relationship between its expression and clinicopathological factors, and the in vitro activity of EG-VEGF transfectants. METHODS: We determined expression levels of EG-VEGF in 113 advanced colorectal cancers resected in our hospital by quantitative PCR, and compared the expression levels and clinicopathological findings by multivariate analyses. RESULTS: The expression of EG-VEGF mRNA was positive in 31 cancers and negative in 82 cancers. We found that compared with the negative expression of the EG-VEGF gene, its positive expression was more frequently associated with hematogenous metastasis, and was associated with a poorer survival rate. In addition, EG-VEGF transfectants showed a higher degree of in vitro tubular formation than control cells. CONCLUSIONS: We speculate that, in colorectal cancers, the EG-VEGF gene functions as an important factor in angiogenesis in primary and metastatic lesions, and consider that it is useful as a novel prognostic factor. EG-VEGF molecule-targeted therapy has the potential for improving survival rates.     

PTEN’s regulation of VEGF and VEGFR1 expression and its clinical significance in myeloid leukemia

Phosphatase and tensin homolog (PTEN) acts as a novel tumor suppressor gene. PTEN protein plays an important role in regulating proliferation, apoptosis, invasion, and migration of many cancer cells. PTEN also modulates angiogenesis mediated by vascular endothelial growth factor (VEGF) via down-regulating PI3K/Akt pathway in many solid tumors. However, the effects of PTEN on VEGF and VEGFR1 (FLT1)-mediated angiogenesis, migration, invasion of leukemia cells, and its clinical significance are still unknown in myeloid leukemia. Therefore, we investigated the effect of PTEN on PI3K/Akt and VEGF/FLT1 pathways by transfecting wild-type PTEN gene to induce high expression of wild-type PTEN gene and protein in chronic myelogenous leukemia cell line K562 cells. We also observed the correlation between the expression levels of PTEN and VEGF/FLT1 and its clinical significance in myeloid leukemia patients. We found that the expression reconstitution of wild-type PTEN had significant effect on inhibiting proliferation, migration, and invasion abilities of K562 cells via down-regulation of Akt phosphorylation and inhibition of VEGF/FLT1 expression. In myeloid leukemia patients, a negative correlation was found between the expression level of PTEN mRNA and that of VEGF and FLT1 mRNA. Down-regulation of PTEN expression accompanied by up-regulation of VEGF and FLT1 mRNA indicated a higher tendency of extramedullary disease in acute myeloid leukemia patients. In conclusion, PTEN could modulate the function of VEGF/VEGFR signaling pathway down-regulation of Akt phosphorylation and that PTEN would be a candidate target to be addressed for inhibiting angiogenesis along with the treatment of myeloid leukemia.     

Eukaryotic initiation factor-4E in superficial and muscle invasive bladder cancer and its correlation with vascular endothelial growth factor expression and tumour progression

Vascular endothelial growth factor (VEGF) is an important factor mediating tumour angiogenesis. VEGF mRNA is differentially expressed in bladder cancer with high expression in superficial tumours (stage pTa and pT1) contrasting with low expression in muscle invasive tumours (stage > or = pT2). To investigate mechanisms regulating VEGF expression in bladder cancer, VEGF mRNA and protein were measured in normal bladder (n = 12) and primary bladder cancers (n = 57). VEGF protein levels correlated with mRNA expression in normal bladder (r = 0.68, P = 0.02) and bladder cancer (r = 0.46, P = 0.0007). Whilst VEGF mRNA expression was threefold higher in superficial compared to muscle invasive bladder cancers (P = 0.0001) there was no difference in VEGF protein (P = 0.81). Accordingly, the median protein:mRNA ratios increased more than 15-fold with increasing tumour stage (P < 0.0001) suggesting translational regulation. Expression of the eukaryotic initiation factor-4E (elF-4E), a factor implicated in the translational regulation of VEGF, was greater in tumours than normal bladder (P < 0.0001) and correlated with VEGE protein:mRNA ratios (n = 43, r = 0.54, P = 0.0004) pointing to its role in the regulation of VEGF. In superficial tumours (n = 37) high expression of eIF-4E was associated with a poor prognosis and reduced stage progression-free survival (P = 0.04, Cox proportional hazards model). The study demonstrates that eIF-4E may be involved in translational regulation of VEGF in bladder cancer and might have a role as a prognostic factor in bladder cancer.     

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     

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.     

Expression of vascular endothelial growth factor and its receptor KDR (kinase domain-containing receptor)/Flk-1 (fetal liver kinase-1) as prognostic factors in human colorectal cancer

Background. To clarify the clinical significance of the expression of vascular endothelial growth factor (VEGF) and its receptor, kinase domain-containing receptor (KDR) in colorectal cancer, we evaluated the relationship between the expression of VEGF and KDR, and the microvessel counts and clinicopathological factors in colorectal cancer. Methods. A total of 259 specimens from sequential colorectal cancer patients who had undergone surgery were examined by the avidin-biotin peroxidase complex method, using anti-human VEGF, anti-human KDR, and anti-human von Willebrand factor antibodies. Results. The incidence of VEGF expression in the tumor cells of the patients with liver metastasis was significantly higher than that in the tumor cells of the patients without liver metastasis (67% vs 44%). The microvessel count at the tumor invasive edge in the patients whose tumor cells were positive for VEGF was significantly higher than that in the patients whose tumor cells were negative for VEGF (33.0 ± 7.8 vs 28.0 ± 7.9); the significant difference in microvessel counts was greater when there was a combination of VEGF and KDR expression. The overall survival rate of patients positive for VEGF was significantly (P = 0.0276) lower than that of those who were negative for VEGF. Although there was no significant difference (P = 0.0743) in the survival rates after potentially curative resection according to VEGF expression, the survival rate of the patients positive for both VEGF in tumor cells and KDR in endothelial cells was significantly (P = 0.0026) lower than that in the patients who were negative for VEGF and/or KDR. In addition, multivariate analysis revealed that the expression of both VEGF and KDR was an independent prognostic factor even after potentially curative resection. Conclusion. VEGF may be implicated in the definition of the malignant phenotype of colorectal cancer via tumor angiogenesis. VEGF and its receptor KDR expression in tumorous tissues could be useful prognostic factors in colorectal cancer. Received: September 18, 2000 / Accepted: August 27, 2001     

Vascular endothelial growth factor is up-regulated in the early pre-malignant stage of colorectal tumour progression.

Angiogenesis is an essential requirement for the development, progression and metastasis of malignant tumours. Studies on transgenic mouse models have shown that angiogenesis begins in the pre-malignant phase of oncogenesis, when dysplastic lesions acquire an increased microvasculature. To investigate the relationship between the expression of vascular endothelial growth factor (VEGF) and colorectal tumour progression, we have studied VEGF expression level and splice variant pattern by semi-quantitative RT-PCR and the cellular source of VEGF expression by in situ hybrization (ISH) in a range of lesions that modelled the tumour-development pathway from normal colon to invasive colorectal adenocarcinomas. Colonic adenomas showed a statistically significant up-regulation of VEGF expression over normal tissues, with a further increase during the development of adenocarcinomas. Tumour cells formed the major source of VEGF expression, with a minor contribution from mononuclear cells in the tumour stroma and enhanced expression in tumour cells around necrotic regions. The comparable expression level in both the in situ and invasive components in the same tumours indicated that a high VEGF expression capacity had been acquired prior to establishment of the invasive phenotype. Our findings support activation of VEGF as the molecular basis for the discrete induction of angiogenesis in the pre-malignant phase of colorectal tumour development.