乳腺肿瘤超声造影与微血管密度的相关性探讨

[目的]探讨超声造影微血管显像与微血管密度（MVD）的相关性及其在乳腺肿瘤中的诊断价值。[方法]选取乳腺肿块患者70例,术前一周行超声造影检查,利用时间—强度曲线评估肿块性质;术后病理标本行CD34免疫组化标记,观察肿块微血管分布,分析超声造影与MVD相关性。[结果]良恶性肿瘤灌注类型明显不同。良恶性肿瘤时间强度—曲线形态特征不同,两者各定量值均有显著差异（P〈0.05）。免疫组化显示良恶性肿瘤排列特征不同,MVD有显著性差异（P=0.007）。良恶性肿瘤峰值强度与MVD均有明显相关性,且恶性肿瘤曲线下面积与MVD具有一定相关性。[结论]乳腺超声造影在一定程度上可以反映肿块微血管分布特征,有助于乳腺良恶性肿瘤的鉴别。     

乳腺肿块超声造影增强强度与病理微血管密度的相关性

目的 研究声诺维超声造影对乳腺肿块增强强度与病理微血管密度(MVD)的相关性.方法 应用超声造影技术观察38例乳腺肿块微血管灌注情况,计算机定量测量肿块增强强度,对比良恶性肿瘤的造影强度特征,术后标本进行抗Ⅷ因子免疫组化染色,测量MVD.结果 乳腺肿块超声造影增强强度与病理MVD有较好的相关性(r=0.802,P＜0.005),造影强度与MVD恶性组均大于良性组.结论 声诺维超声造影有助于鉴别诊断乳腺良恶性肿瘤及评估乳腺癌的预后.     

乳腺浸润性导管癌的超声造影增强参数与微血管密度相关性研究

目的探讨乳腺浸润性导管癌(invasive ductal carcinoma,IDC)超声造影增强参数与病理微血管密度(microvessel density,MVD)的相关性。方法对52例经手术或穿刺活检病理证实的IDC患者行超声造影,记录各项造影参数;对术后病理标本HE染色进行肿瘤病理分级,应用CD34行免疫组化检测MVD;分析超声造影参数与MVD的相关性。结果 52例IDC中,高分化组25例,低分化组27例。高分化组、低分化组的MVD分别为(2.87±0.97)%和(4.32±1.07)%,不同分化程度组间MVD差异有统计学意义(P<0.001)。低分化组峰值强度及曲线下面积均高于高分化组(P<0.05),且峰值强度、曲线下面积均与MVD显著相关(P<0.05),曲线下面积与MVD最相关(r=0.89,P<0.001)。结论超声造影增强参数与病理MVD有相关性,其有助于评估IDC的分化程度。     

超声造影在肾脏占位性病变诊断中的研究进展

肾脏肿瘤是泌尿系统常见肿瘤之一,且多为恶性,近年来其发病率呈上升趋势。目前超声造影检查已被广泛应用于临床上进行肾脏良恶性肿瘤鉴别,超声造影能清晰显示组织及肿瘤内的血管及微血管,动态观察正常组织及肿瘤组织血流灌注状态,在肾脏实性及囊性占位性病变中具有一定诊断价值。本文将就超声造影在肾脏肿瘤的现状及其临床应用的研究进展进行阐述。      

晚期肝癌低频超声空化治疗的超声血管造影表现

目的观察晚期肝癌患者低频超声空化治疗的超声血管造影表现。方法晚期肝癌患者12例(其中原发性肝癌7例,转移性肝癌5例),行低频超声空化治疗。治疗前、后进行超声微血管造影。结果通过超声血管造影能够清晰地看到肿瘤微血管。低频超声空化治疗后肿瘤血管造影强度低于治疗前,且治疗后病灶内出现低回声区。结论低频超声空化治疗具有毁损肿瘤血管的作用;超声微血管造影可以用来评估低频超声空化治疗后肿瘤血管的破坏情况。     

微血管模式、密度及影像学参数对涎腺腺样囊性癌预后的关系

目的探讨微血管模式、密度以及影像学参数与涎腺腺样囊性癌预后的相关性。方法收集涎腺腺样囊性癌患者148例,免疫组化染色方法检测血管内皮细胞CD31、CD105单克隆抗体表达及检测涎腺肿瘤组织的微血管密度(MVD),比较CT灌注参数、微血管密度(MVD)参数在良恶性肿瘤之间的差异及相关性。结果 CD31在恶性肿瘤组中的表达明显高于良性肿瘤组,但两组之间比较差异无统计学意义(P>0.05);CD105在恶性肿瘤组中的表达明显高于良性肿瘤组,但两组之间比较差异无统计学意义(P>0.05);恶性肿瘤组灌注参数BF、BV、PS值明显高于良性组,差异比较具有统计学意义(P<0.05),而两组的MTT参数比较差异不具有统计学意义(P>0.05);采用Spearman分析肿瘤各灌注各参数值与MVD的相关性,结果显示BF、PS、BV、MTT与MVD之间呈正相关性。结论 CT灌注参数可较准确地定量分析肿瘤血流灌注状态,微血管密度(MVD)、CD105可特异性标记肿瘤新生血管内皮细胞,在涎腺腺样囊性癌的预后的评价中发挥着有积极作用。     

超声造影在眼部良恶性肿瘤诊断中的应用

目的：研究超声造影在眼部良恶性肿瘤诊断中的应用及效果。方法回顾性分析20例眼部肿瘤患者的临床资料、超声造影结果及病理诊断结果,总结眼部良恶性肿瘤通过超声造影进行诊断的可行性及价值。结果20例患者超声造影声像图与二维超声、彩色多普勒超声声像图比较存在不同征象。结论超声在临床中具有无创、可重复性以及经济等特点,彩色多普勒超声、二维超声结合超声造影在眼部良恶性肿瘤声像图中存在不同征象,在提升肿瘤定位和定性方面具有非常重要的价值。     

超声造影对高强度聚焦超声治疗腹腔恶性肿瘤的疗效评价

目的:探讨超声造影对高强度聚焦超声(HIFU)治疗腹腔恶性肿瘤疗效评价的应用价值.方法:选择8例腹腔恶性肿瘤病例.HIFU治疗前后行超声造影检查,观察瘤体大小、血流信号变化.结果:超声造影能清楚显示肿瘤大小及内部血流信号.治疗前动脉期呈不同程度增强.HIFU治疗后6例患者肿瘤内无增强,2例患者肿瘤内仍见造影剂增强.结论:超声造影能准确显示HIFU治疗腹腔恶性肿瘤的消融范围及程度,可作为评价治疗效果的可靠方法.     

实时超声造影对乳腺肿瘤BI-RADS分类的诊断价值分析

目的分析实时超声造影对乳腺肿瘤乳腺影像报告与数据系统(BI-RADS)分类的诊断价值。方法以120例乳腺实性肿块患者为研究对象。在常规超声的基础上行造影检查。分析超声造影检查的良、恶性肿瘤的增强程度、增强范围变化、增强边缘、灌注方式、造影剂分布和肿瘤血管图像特征情况,比较常规超声和超声造影的BI-RADS分类情况,并以病理检查为金标准评价比较两种检查方法的诊断能力。结果超声造影检查对于良性和恶性肿瘤的增强程度、增强范围变化、增强边缘、灌注方式、造影剂分布和肿瘤血管情况差异均具有统计学意义(P<0.05);常规超声和超声造影检查的BI-RADS分类情况差异不具有统计学意义(P>0.05);超声造影检查的准确度和对恶性肿瘤的灵敏度高于常规超声(P<0.05),两种检查方法对恶性肿瘤的特异度差异无统计学意义(P>0.05),但超声造影检查对恶性肿瘤的特异度略高于常规超声检查。结论造影检查可在常规超声基础上提高对乳腺肿瘤BI-RADS分类准确性,提高了对良恶性肿瘤的鉴别诊断准确度、特异度和灵敏度,为临床进一步诊治提供依据,但仍需扩大样本量进一步从超声检查操作和图像分析能力的规范性方面展开研究。     

超声造影在良恶性子宫肿瘤诊断中的临床价值

目的探讨超声造影在良恶性子宫肿瘤诊断方面的临床应用价值。方法采用低机械指数灰阶谐波超声造影技术,分析经手术及病理证实的62例子宫肿瘤的超声造影强化特点并行时间-强度曲线分析。结果病理诊断良性病变34例,恶性病变28例,超声造影诊断符合率为90.3%。子宫良、恶性肿瘤的超声造影强化方式及时间-强度曲线形态各具不同特征,造影参数中始增时间、达峰时间、峰值强度在子宫良、恶性肿瘤组比较,差异有统计学意义(P<0.05)。结论超声造影能显示肿瘤血流灌注情况,可用于提高子宫肿瘤良恶性鉴别诊断。     

妇科恶性肿瘤组织诱导血管形成与临床预后因素的相关性

目的探讨妇科恶性肿瘤组织诱导兔角膜血管形成分级可否作为判断患者预后的一项监测指标,并对妇科三种恶性肿瘤之间的生物学行为进行评价。方法分析１１例卵巢恶性肿瘤,１０例乳腺癌,９例子宫内膜癌诱导兔角膜血管形成分级与临床预后因素之间的关系,并对三种恶性肿瘤诱导兔角膜血管生成活性进行比较。结果Ⅱ级血管形成在临床Ⅱ～Ⅳ期,淋巴结阳性或有转移灶的病例明显高于临床Ⅰ期,淋巴结阴性或无转移灶的病例,差异有极显著性（Ｐ＜０．０１）。血管形成分级与组织学分级及肿瘤直径之间差异无显著性（Ｐ＞０．０５）。血管形成活性卵巢恶性肿瘤为“＋＋＋”,乳腺癌和子宫内膜癌分别为“＋＋”。结论瘤组织诱导兔角膜血管形成分级可作为判断肿瘤患者预后指标之一。血管形成活性在这三种恶性肿瘤排列顺序与他们的生物学行为相一致,其预后卵巢恶性肿瘤最差。     

星形细胞肿瘤CT灌注成像参数与MVD的相关性

目的评价星形细胞肿瘤CTP参数与MVD之间的相关性。方法选择我院神经外科53例脑肿瘤患者,经手术和病理学证实为星形细胞肿瘤者纳入研究对象。CTP采用GE LightSpeed 64层螺旋CT机进行灌注扫描,在AW4.2P后处理工作站对原始数据进行后处理,测定肿瘤最大灌注区和对侧正常脑组织的CBF、CBV、MTT及PS值。手术获取脑肿瘤标本,进行组织病理学分级和MVD测定。结果高、低级别星形细胞肿瘤的CBF、CBV、PS和MVD值均显著高于相对应正常侧脑组织(P<0.01),而MTT值的差异无统计学意义(P>0.05)。AA-GBM组的CBF、CBV、PS及MVD值均显著高于LGA组(P<0.01),而MTT值差异无统计学意义(P>0.05)。星形细胞肿瘤CTP参数CBF、CBV、PS与MVD均有显著线性正相关(r＝0.819,0.862,0.776,P<0.01),以CBV值最强,而MTT与MVD无相关性(r＝-0.320, P>0.05)。结论CTP参数CBF、CBV及PS值对星形细胞肿瘤血管生成的评价具有很高的准确性。     

促血管生成素表达与人脑胶质瘤血管生成的关系研究

目的:研究促血管生成素(angiopoie-tins,Angs)蛋白表达水平与血管内皮生长因子(vascular endothelial growth factar,VEGF)和肿瘤内微血管密度(microvascular density,MVD)的关系,探讨其在人脑胶质瘤血管生成中的作用。方法:采用免疫组化方法检测42例人脑胶质瘤组织中Ang-1、Ang-2和VEGF的蛋白表达水平,并以抗CD34单克隆抗体显示血管内皮细胞,根据CD34阳性的血管计数来判定MVD。结果:42例人脑胶质瘤中,Ang-1+肿瘤的MVD比Ang-1-肿瘤高,但两者差异无统计学意义,P=0·156;Ang-2-和Ang-2+平均MVD分别是27·67和49·63,Ang-2+肿瘤MVD显著高于Ang-2-肿瘤,P=0·000。VEGF阳性表达时,Ang-2+肿瘤平均MVD显著高于Ang-2-肿瘤,分别为56·00和36·75,P=0·001;而VEGF阴性组中,Ang-2+肿瘤平均MVD与Ang-2-肿瘤几乎相等,分别为53·17和47·36,P=0·109。随胶质瘤恶性程度增加,Ang-1和Ang-2阳性表达率均升高,但Ang-2升高更明显,不同级别间Ang-2表达水平差异有统计学意义。结论:Ang-2高表达与人脑胶质瘤血管新生密切相关,Ang-2可以作为评价胶质瘤血管生成及恶性程度的一个重要指标。VEGF存在时,Ang-2过表达可促使肿瘤血管生成。肿瘤防治杂志,2005,12(19):1472-1475     

Expression of CD34 in gastric cancer and its correlation with histology, stage, proliferation activity, p53 expression and apoptotic index

The formation of new blood vessels is essential for tumor growth and progression. Until today there are only few studies of the immunohistochemical assessment of angiogenesis in gastric cancer by the evaluation of the expression of CD34 antigen. The aim of this study was to analyze the relationship between microvessel density (MVD) expressed as the mean count of CD34 immunostained vessels and clinicopathologic features of gastric tumors (the histological type according to the Lauren classification, tumor grade G; presence of lymph node metastases N; depth of tumor invasion; stage of disease (UICC-AJCC 1988 1992), p53 expression, tumor cell proliferative activity described as the Ki67 labelling index and apoptotic index of tumor cells TUNEL method). We assessed formalin-fixed, paraffin-embedded tissue samples obtained during potentially radical gastrectomy from 58 patients with primary gastric adenocarcinoma. The representative tissue blocks from each tumor were used for the immunohistochemical assay and examined by two pathologists independently. MVD was counted in five tumor areas of the most intensive neovascularization (x 200 field by light microscopy) and the mean counts were recorded. The mean MVD (CD34 expression value+/-SD) in this study was 43,15+/-19,8 per x 200 field. The study demonstrated the statistically significant correlation between MVD and two main histological parameters: tumor grading (p < 0.001) and tumor histological type according to Lauren s classification (p<0.05). In well and moderately differentiated tumors (G1/2) MVD was significantly lower in comparison to the group of poorly differentiated cancer G3 (mean value: 31,62 vs. 49,89). MVD was higher in diffuse type of gastric cancer comparing to intestinal type (50.05+/-19,03 vs. 39.17+/-20,09). However, the authors failed to find a significant correlation between MVD and other investigated histopathological features in malignant gastric tumors. The close relationship between CD34 immunostaining, gastric cancer tumor vascularity and main histological parameters was shown in this study. It can be stated that analysis of expression of angiogenesis in gastric cancer may be helpful for better estimation of hematogenous recurrence and the selection of the group of patients for adjuvant antiangiogenic treatment.     

Heterogeneity of angiogenesis and blood vessel maturation in human tumors: implications for antiangiogenic tumor therapies

Microvessel density (MVD) counting techniques have been widely used to assess the vasculature in tumors. MVD counts assess the presence of blood vessels but do not give an indication of the degree of angiogenesis and the functional status of the tumor neovasculature. To analyze angiogenesis and the functional status of the tumor vascular bed, we have quantitated endothelial cell proliferation and the recruitment of pericytes in human tumors [glioblastomas (n = 30), renal cell carcinomas (n = 22), colon carcinomas (n = 18), mammary carcinomas (n = 24), lung carcinomas (n = 15), and prostate carcinomas (n = 19)]. These findings were compared to the physiological angiogenesis in the cyclic bovine ovarian corpus luteum. Tissue sections were examined applying double-labeling immunohistochemical techniques to detect proliferating endothelial cells and to colocalize endothelial cells and pericytes. The following parameters were quantitated: (a) MVD count; (b) proliferating capillary index (PCI); (c) proliferating tumor versus endothelial cell index; and (d) microvessel pericyte coverage index (MPI). Based on endothelial cell proliferation, angiogenesis was found to be present in all tumors with characteristic and significant differences between the tumor types (glioblastomas, PCI = 9.6 +/- 6.1%; renal cell carcinomas, PCI = 9.4 +/- 5.2%; colon carcinomas, PCI = 7.8 +/- 5.2%; mammary carcinomas, PCI = 5.0 +/- 4.8%; lung carcinomas, PCI = 2.6 +/- 2.5%; prostate carcinomas, PCI = 2.0 +/- 1.4%). There was a considerable degree of heterogeneity in the intensity of angiogenesis within each tumor group, as indicated by large standard deviations. Even in the most angiogenic tumors, angiogenesis was found to be 4 to 20 times less intense as compared with the physiological angiogenesis in the growing ovarian corpus rubrum (PCI = 40.6 +/- 6.2%). Varying degrees of pericyte recruitment to the tumor microvasculature were determined in the different tumor types (glioblastomas, MPI = 12.7 +/- 7.9%; renal cell carcinomas, MPI = 17.9 +/- 7.8%; colon carcinomas, MPI = 65.4 +/- 10.5%; mammary carcinomas, MPI = 67.3 +/- 14.2%; lung carcinomas, MPI = 40.8 +/- 14.5%; prostate carcinomas, MPI = 29.6 +/- 9.5%). The data demonstrate distinct quantitative variations in the intensity of angiogenesis in malignant human tumors. Furthermore, the varying degrees of pericyte recruitment indicate differences in the functional status of the tumor vasculature in different tumors that may reflect varying degrees of maturation of the tumor vascular bed.     

卵巢癌组织中VEGF及MVD表达及其临床意义

目的 分析微血管密度(MVD)以及卵巢上皮性肿瘤血管内皮生长因子(VEGF)的表达与卵巢癌临床病理因素的关系及两者的相关性.方法 选取手术切除的卵巢上皮性肿瘤标本88例以及正常卵巢组织标本35例,采用免疫组化染色方法检测所有标本中VEGF及MVD的表达情况,分析两者相关性及与卵巢上皮性肿瘤临床病理因素的关系.结果 VEGF在卵巢癌组织中的表达阳性率为92.0％及MVD平均值为(30.26±8.69),显著高于良性卵巢上皮性肿瘤组织VEGF的阳性表达率[52.6％,(11.52±3.46)] (P ＜0.05);而良性卵巢上皮性肿瘤组织中VEGF阳性表达率及MVD平均值均高于正常对照组(P＜0.05).VEGF阳性表逸的卵巢癌组织中MVD平均值显著高于VEGF阴性表达者,VEGF阳性表达与MVD平均值呈正相关(P＜0.05).卵巢癌组织中VEGF阳性表达与肿瘤临床分期及细胞分化程度存在明显相关性(P＜0.05),而与肿瘤直径、组织学类型以及患者年龄无明显相关性(P＞0.05).MVD与肿瘤临床病理特征无明显相关性(P＞0.05).结论 VEGF及MVD均能反映卵巢上皮性肿瘤的良恶性和恶性进展程度,并可能成为卵巢癌临床生物学治疗的参考指标.     

卵巢交界性肿瘤血管内皮生长因子表达和微血管密度的研究

背景与目的:血管生成是实体肿瘤生长、侵袭、扩散转移的关键,微血管密度(microvesselofdensity,MVD)可反映肿瘤的血管形成情况。血管内皮生长因子(vascularendothelialgrowthfactor,VEGF)是具有重要意义的促血管生长因子,它与肿瘤的生长密切相关。本研究检测卵巢交界性肿瘤组织中VEGF的表达和MVD,探讨它们与临床病理特征及预后的关系。方法:采用免疫组化SP法和原位杂交技术检测69例卵巢交界性肿瘤、18例卵巢良性肿瘤和27例卵巢恶性肿瘤组织中VEGF蛋白及VEGFmRNA的表达,用FⅧ因子单克隆抗体标记新生血管内皮,计数并计算MVD。结果:VEGF蛋白、VEGFmRNA在卵巢交界性肿瘤组织中的表达均介于卵巢良性肿瘤与卵巢恶性肿瘤之间,其结果差异均有显著性(P<0.05);也与卵巢交界性肿瘤的临床分期、MVD值密切相关(P<0.05);但VEGF与卵巢交界性肿瘤的组织分型、有无腹腔种植无关(P>0.05)。结论:VEGF与卵巢肿瘤的生长、侵袭、转移密切相关;检测VEGF有助于判断卵巢肿瘤的恶性程度,为判断卵巢交界性肿瘤患者的预后提供依据。     

Angiogenesis and Lymphangiogenesis in Salivary Gland Adenoid Cystic Carcinoma and Mucoepidermoid Carcinoma

Background and Purpose: This study aimed to investigate the immunohistochemical expression of CD31 and podoplanin in order to examine angiogenesis and lymphangiogenesis, respectively in common malignant tumors of salivary glands. Materials and Methods: Forty formalin-fixed, paraffinated blocks (20 adenoid cystic carcinoma and 20 mucoepidermoid carcinoma blocks) were selected from the medical archives of Amir A’lam Hospital of Tehran, Iran. Sections from the blocks were stained by CD31 and D2-40 markers via immunohistochemistry. Clinical and demographic information was extracted from the patients’ records. Findings: There was a significant difference between tumors in terms of intratumoral microvessel density (MVD) (P< 0.001), total MVD (P< 0.001), and intratumoral lymphatic vessel density (LVD) (P= 0.011). In mucoepidermoid carcinoma, intratumoral MVD and LVD were greater than peritumoral MVD and LVD (P= 0.001 and P< 0.001, respectively). In mucoepidermoid carcinoma, there was no relationship between histological grade with MVD (total, intratumoral or peritumoral) or LVD (total, intratumoral or peritumoral) (P> 0.05). A similar finding was reported with respect to the histopathological grade of adenoid cystic carcinoma (P> 0.05). Conclusion: The higher level of angiogenesis and lymphangiogenesis in mucoepidermoid carcinoma, specifically at the center of tumor, compared to adenoid cystic carcinoma, may be attributed to differences in the clinical behaviors and metastasis of tumors. Moreover, considering the high LVD at the center of tumor in mucoepidermoid carcinoma and infrequency of metastasis to regional lymph nodes in adenoid cystic carcinoma, it can play a significant role in metastasis to regional lymph nodes.     

Tumor vascularity: a histological measure of angiogenesis and hypoxia

In this study we sought to clarify the relationship between tumor vascularity, hypoxia, and angiogenesis in human cervix tumors. Two hypotheses were established: first, that measurement of tumor vascularity can provide a histological assessment of both hypoxia and angiogenesis; and second, that expression of angiogenesis-related proteins will provide a surrogate measure of tumor hypoxia. To test the first hypothesis, we studied the prognostic significance of tumor vascularity measured as both intercapillary distance (ICD; thought to reflect tumor oxygenation) and microvessel density (MVD; the hotspot method that provides a histological assessment of tumor angiogenesis). The relationship was also examined of tumor hypoxia, measured using an Eppendorf needle electrode [percentage of values less than 5 mm Hg (HP5)], with ICD and MVD. To test the second hypothesis we examined the relationship between HP5 and the expression of angiogenesis-associated proteins [vascular endothelial growth factor (VEGF) and platelet-derived endothelial cell growth factor (PD-ECGF)]. All of the biological measurements were made on pretreatment tumors. Analysis of data was carried out using log-rank statistics, Cox multivariate analysis, and Spearman's rank correlation. Both ICD and MVD were significant independent prognostic factors for local control. Patients with poorly vascularized tumors (long ICD) had poor local control (P = 0.042). However, patients with poorly vascularized tumors, measured as low MVD, had good local control (P = 0.036). For 107 patients in whom both of the measurements were obtained on the same tumor sections, ICD and MVD provided independent prognostic information in multivariate analysis. There was a significant correlation between tumor hypoxia and ICD (P < 0.005) but not MVD (P = 0.41). There was no relationship between hypoxia and the expression of angiogenic factors (VEGF, PD-ECGF). These analyses show that measurement of tumor vascularity can provide different biological information that is dependent on the method used. It is, therefore, important that studies measuring vascularity should include an appropriate definition. There is no relationship between hypoxia and angiogenesis in advanced carcinoma of the cervix and examining the levels of angiogenic proteins may not have a role in assessing hypoxia in cervix cancer.     

Angiogenesis and p53 expression in the colorectal adenoma-carcinoma sequence

Angiogenesis, the formation of new vessels, is essential for tumor growth and metastasis. Mutations of p53 tumor suppressor gene are frequent and play an important role in colorectal oncogenesis. A role of p53 as an angiogenesis inhibitor has also been proposed. We evaluated angiogenesis and p53 expression in 16 hyperplastic polyps, 35 solitary tubular and tubulovillous adenomas, and 47 cases of sporadic colorectal carcinomas arising on the basis of preexisting adenomas, with standard immunohistochemical techniques. The mean microvessel density (MVD) in carcinomas was significantly higher compared with the respective adenomatous part of the same tumor (27.9 vs. 7; P=0.0001). Linear regression analysis of MVD between cancerous and adenomatous areas showed a significant correlation (P = 0.0001, r = 0.56), raising the possibility that carcinomas arising from better vascularized adenomas might show increased vascularity. The MVD was significantly higher in stage C compared with stage A cases (P=0.04). p53 positivity was detected in 26 of 47 cancerous (55%) and in 14 of 47 adenomatous areas (30%; P = 0.0002). All carcinomas arising from p53-positive adenomas were also p53 positive. p53 positivity associated with a higher MVD in adenomas (P = 0.02), but not in carcinomas (P = 0.78). We conclude that angiogenesis and p53 play a critical role in colorectal neoplasia, and the process of malignant transformation in tumors arising from highly angiogenic adenomas, particularly those carrying p53 mutations, is accelerated with rapid tumor progression from stage to stage, indicating a more aggressive tumor phenotype.