超微血管成像对动脉硬化斑块内新生血管的预测价值

目的 探讨超微血管成像模式(superb microvascular imaging,SMI)对颈动脉粥样硬化斑块内新生血管(intra-plaque neovascularization,IPN)检出的预测价值.方法 全面检索Cochrane Library、PubMed、CBM、CNKI数据库中有关超微血管成像模式...     

三维超声及微血管密度在卵巢浆液性肿瘤病理性质中的研究

目的探讨良、恶性卵巢浆液性肿瘤三维超声形态特征及三维能量多普勒(3D-CPA)血流特点,并与病理微血管密度(MVD)进行相关性研究,为临床浆液性肿瘤的诊断提供依据。方法选择76例经手术切除的卵巢浆液性肿瘤患者,年龄26~71岁,平均年龄48.7岁。依据术后病理性质分为良性组(30例,病理结果为良性浆液性囊腺瘤,囊内可见分隔或乳头样实性组织,不包括单纯性浆液性囊腺瘤)、交界性组(24例,病理结果为交界性浆液性囊腺瘤)、Ⅰ期癌组(22例,病理结果为浆液性囊腺癌,国际妇产科联盟卵巢癌分期为Ⅰ期)。术前均经三维超声对肿瘤形态和血流进行观察,比较肿瘤直径、分隔数、分隔厚度、实性组织切面总面积、血流分级、血管指数(VI)。所选病例均进行免疫组织化学分析,计数MVD,研究超声测量结果与MVD的相关性。结果 3组之间分隔数、分隔厚度比较,良性组交界性组及Ⅰ期癌组(P0.05),交界性组与Ⅰ期癌组差异无统计学意义;3组肿瘤内实性组织切面总面积比较,良性组交界性组Ⅰ期癌组(P0.05),肿瘤直径差异无统计学意义(P0.05)。3D-CPA血管分级良性组以Ⅰ级血流多见,交界性组、Ⅰ期癌组以Ⅱ、Ⅲ级尤其以Ⅱ级多见;VI值比较,良性组交界性组Ⅰ期癌组(P0.05)。MVD 3组间存在差异,相关性分析显示,分隔数、分隔厚度、实性组织切面总面积与MVD呈正相关(r=0.247、0.469、0.717,P0.05),其中,分隔厚度、实性组织切面总面积相关性较好。MVD与肿瘤直径无显著相关性。交界性组、Ⅰ期癌组3D-CPA血管分级与MVD呈正相关(r=0.52、0.57,P0.05),VI与MVD亦呈正相关(r=0.49、0.58,P0.05)。结论三维超声观察卵巢肿瘤的形态及血流信号可提高对卵巢浆液性肿瘤良恶性的初步鉴别,为临床诊治提供依据。     

功率多普勒成像与MVD、VEGF检测乳腺肿块血管生成的相关性研究

目的探讨功率多普勒成像（PDI）与微血管密度（MVD）、血管内皮生长因子（VEGF）检测乳腺肿块血管形成的相关性并评价其临床应用价值。方法选择2005年9月～2006年3月山西医科大学第二医院乳腺科乳腺肿块患者39例．均为女性．年龄22～71岁,平均年龄44．5岁（良性组39．2岁,恶性组48．8岁）。良性17例,恶性22例。对全部患者行超声检测,采用计算机Photoshop 7．0软件对肿块功率多普勒血流信号进行定量分析．测定彩色像素密度（CPD）;用抗CD34因子及抗VEGF因子免疫组织化学染色测定肿块MVD及VEGF阳性表达率．对CPD与MVD的相关性进行分析。结果恶性组CPD、MVD及VEGF阳性表达率较良性组高．两者差异有显著统计学意义（P〈0．01）,CPD与MVD间具有良好相关性（r=0．822．P〈0．01）。结论PDI所测CPD可较好反映乳腺肿块血流情况,有助于乳腺疾病的鉴别诊断,与MVD计数、VEGF测定相结合,能全面反映肿瘤血管生成状态。     

肝癌微血管密度、微血管面积和Piezo1的表达与微血管侵犯的相关性

目的:探讨肝癌组织中微血管密度(microvascular density,MVD)、微血管面积(microvascular area,MVA)以及Piezo1的表达水平预测肝癌微血管侵犯(microvascular invasion,MVI)的临床价值.方法:应用免疫组织化学方法检测38例病理证实为肝癌患者的肝癌组织的CD34以及Piezo1的表达情况,计算基于CD34染色的MVD和MVA,分析MVI与MVD,MVA以及Piezo1因子的表达水平的相关性.结果:38例肝癌中,13例有微血管侵犯,定义MVI(+)组,25例无微血管侵犯,定义MVI(?)组.MVI(+)组的MVA及MVD均高于MVI(?)组,两组间差异有统计学意义(P=0.007,P=0.011).MVD和MVA联合预测MVI的敏感性和特异性为100％和64％,较单一指标效能高.Piezo1在肝癌MVI(+)组阳性率高于MVI(?)组,两组间差异有统计学意义(P=0.032).结论:MVD,MVA以及Piezo1的表达水平均与肝癌MVI具有一定的相关性,可以作为辅助诊断微血管侵犯的指标,Piezo1可以作为潜在的限制MVI的治疗靶点.     

超微血管成像技术在类风湿性关节炎患者手腕关节中的应用价值

目的比较超微血管成像技术(SMI)和能量多普勒(PDUS)在评估类风湿性关节炎(RA)患者急性期和临床缓解期手腕关节滑膜内血管增生的应用价值。方法选择经临床诊断RA患者80例,其中男性25例,女性55例;年龄43~78岁,平均年龄55.5岁;急性期35例,临床缓解期45例。急性期患者中男性10例,女性25例;年龄43~76岁,平均年龄55.3岁。临床缓解期患者中男性15例,女性30例;年龄45~78岁,平均年龄55.6岁。同时采用PDUS和SMI两种超声成像方法检测手腕关节增厚滑膜内的血管增生显示率、血流分级和检查时长,评估血流分级与28个关节的疾病活动度评分(DAS28)的相关性。结果无论是急性期还是临床缓解期患者,SMI较PDUS血流信号显示率(急性期,88.46%vs53.85%;临床缓解期,86.49%vs 54.04%)和血流分级(急性期,3级50.00%vs 11.54%;临床缓解期,3级59.46%vs10.81%)明显增加,检查时长缩短(急性期,4.4 min±0.8 min vs 8.2 min±1.3 min;临床缓解期,4.6 min±0.7 min vs8.5 min±1.4 min)(P <0.05)。经Spearman检验发现,SMI显示血流信号分级与DAS28有较好的一致性(R=0.768、0.723,P=0.011、0.015)。对SMI显示血流信号患者进行强化干预后,血管显示率和血流信号分级均明显减少,DAS28也明显下降(P <0.05)。结论 SMI和PDUS是显示RA手腕关节滑膜内血管增生的重要方法,SMI较PDUS能够更加准确、方便显示血流信号,定量评估血流分级,与炎症活动度有较好的一致性,对指导临床制定正确的干预策略提供重要参考依据。     

超微血管成像联合剪切波弹性成像在乳腺肿瘤患者良恶性鉴别诊断中的应用及其对诊断价值的影响

目的探讨超微血管成像(SMI)联合剪切波弹性成像(SWE)在乳腺肿瘤患者良恶性鉴别诊断中的应用及其对诊断价值的影响。方法选择2016年1月至2017年6月南京江北人民医院83例乳腺肿瘤患者,均为女性,年龄22~74岁。根据乳腺手术及病理活检等证实94个肿瘤,其中良性肿瘤48个(良性组:年龄22~73岁,平均年龄47.23岁;肿瘤直径1.2~5.3 cm,平均直径3.28 cm;乳腺炎性肉芽肿2个,导管内乳头状瘤6个,纤维腺瘤26个,乳腺腺病14个),恶性肿瘤46个(恶性组:年龄25~74岁,平均年龄46.91岁;肿瘤直径1.5~5.6 cm,平均直径3.40 cm;转移癌2个,黏液性乳腺癌3个,浸润性导管癌19个,浸润性小叶癌20个,原位癌2个)。两组均分别接受SWE及SMI检查,统计对比两组SWE检查弹性值(弹性最小值、弹性最大值、弹性平均值)、SWE分型情况、SWE检查相关参数(Ave R、Ave T1、Ratio1)、SMI血流分级、SWE及SMI单独与联合诊断乳腺肿块良恶性价值。结果良性组弹性最小值、弹性最大值、弹性平均值较恶性组小,差异有统计学意义(P0.05);良性组SWE分型1型比率(52.08%)、3型比率(31.25%)较恶性组(2.17%、10.87%)高,4型比率(2.08%)、5型比率(2.08%)、6型率(2.08%)较恶性组(23.91%、30.43%、30.43%)低,差异有统计学意义(P0.05);良性组Ave R、Ave T1、Ratio1较恶性组小,差异有统计学意义(P0.05);良性组SMI血流分级0级比率(18.75%)、Ⅰ级比率(60.42%)较恶性组高,Ⅲ级比率(2.08%)较恶性组低,差异有统计学意义(P0.05);联合诊断灵敏度(95.65%)、准确度(94.68%)较SWE、SMI高,差异有统计学意义(P0.05)。结论 SMI联合SWI可有效鉴别诊断乳腺肿瘤良恶性质,辨别其血流特征及弹性组织性质,提高诊断灵敏度及准确度,减少漏诊及误诊。     

非霍奇金淋巴瘤中的微血管密度及其临床病理意义

目的：探讨非霍奇金淋巴瘤(NHL)中的微血管密度(MVD)及其与NHL恶性程度、免疫学类型、预后的关系；方法：采用生物素标记的荆豆凝集素I(Bio-UEA-I)免疫组化ABC法对102例NHL的MVD进行原位观察和数量分析；结果：MVD随NHL恶性程度的增高而增高，高度恶性组和中度恶性组MVD显著高于低度恶性组MVD；T细胞性NHL中的MVD显著高于B细胞性NHL的MVD；短生存期组的MVD显著高于长生存期组的MVD；结论：NHL中的MVD可作为判断肿瘤恶性程度、免疫学类型及预后估计的有意义的指标，在临床病理中有实际应用价值。     

胃癌组织中CXCR3表达与微血管形成的关系及其临床意义

目的探讨胃癌组织中CXCR3的表达和微血管形成的关系并分析其临床意义。方法采用免疫组化法检测169例胃癌组织中CXCR3蛋白表达和肿瘤间质微血管密度(microvascular density,MVD),分析其相关性及其与胃癌临床病理参数的关系。结果 CXCR3表达在分化程度高(P=0.025)、浸润程度浅(P=0.005)、TNM分期低(P=0.002)及无淋巴结转移(P=0.001)的胃癌患者中更高;MVD在胃癌分化程度低者中更高(P=0.001),与浸润深度、TNM分期及淋巴结转移无关(P0.05)。胃癌组织中CXCR3表达与MVD呈负相关(r=-0.151,P=0.049)。Kaplan-Meier分析发现高表达CXCR3的胃癌患者(P=0.015)和低MVD患者(P=0.047)的生存时间延长。结论胃癌中CXCR3的表达与MVD呈负相关,且与胃癌的浸润、转移相关。     

脑星形细胞瘤微血管密度与临床病理的关系

目的：探讨星形细胞瘤微血管密度与其临床病理的关系。方法：采用免疫组织化学S－P法，对血管内皮细胞行第八因子相关抗原（FⅧRAg）染色，然后测定微血管密度（MVD）。结果：MVD与患者性别、肿瘤生长部位、大小无明显相关；不同病理组织学级别间MVD差异有显著性（P＜0.05)，病理级别越高，MVD越大；瘤周水肿程度不同的星形细胞瘤之间，MVD差异有显著性（P＜0.01)；复发患者MVD高于未复发患者（P＜0.01)。结论：星形细胞瘤MVD与病理级别、术后复发及瘤周组织水肿关系密切，可作为一项有意义的预后指标。     

信号素4D在结直肠癌组织中的表达及其与微血管密度的关系

目的:探讨结直肠癌组织中信号素4D(semaphorin4D,Sema4D)的表达及其与微血管密度(microvessel density,MVD)的相关性.方法:回顾性分析2014至2015年间在云南省肿瘤医院结直肠外科接受结直肠癌根治性手术的61例患者的临床病理资料;采用免疫组织化学SP法检测该组患者的结直肠癌组织标本及其56例癌旁组织中Sema4D蛋白的表达水平;采用微血管密度计数法计数用CD34标记的微血管.结果:Sema4D主要表达于结直肠癌细胞膜及细胞质,癌旁组织细胞质内呈阴性表达.癌组织Sema4D表达阳性率(61/61)明显高于癌旁组织(0/56),差异有统计学意义(x2=113.027,P＜0.001).Sema4D与MVD两者作相关性分析,两者有显著的正相关(r=0.333,P=0.009).MVD表达量在Sema4D表达高低组间存在显著差异(P=0.003).结论:Sema4D在结直肠癌组织高水平表达,且与MVD存在明显的正相关性,提示其有望成为潜在的结直肠癌血管治疗靶点.     

Comparative evaluation of microvessel density determined by CD34 or CD105 in benign and malignant gastric lesions

Microvessel density (MVD) is regarded as a surrogate marker for angiogenesis and has been used for tumor prognosis. In this study, MVD was identified immunohistochemically by monoclonal antibodies against CD105 and CD34 in the tissues representing gastric carcinoma, chronic gastritis, and hyperplastic polyps, and the results were correlated with clinicopathologic features. The expression of CD105 in the microvessels within benign lesions was barely visible, and MVD was markedly lower than that determined by CD34. CD34 was strongly expressed in the microvessels within hyperplastic polyps and tissues with gastritis. In gastric carcinoma, CD105 expression in microvessels was as high as the MVD, compared with benign lesions. CD105 stained well-formed mature and newly formed immature vessels within the cancer mass. Correlation analysis showed that MVD determined by CD105 correlated with blood vessel invasion, distant metastasis, and formation of ascites. Survival analysis demonstrated an inverse correlation between MVD count and overall survival: patients with MVD counts of 32 or higher survived for a much shorter time than those with counts lower than 32. Multivariate analysis confirmed that MVD determined by CD105 was an independent prognostic factor for survival. Microvessel density determined by CD34 inversely correlated with overall survival, but it did not correlate with other clinicopathologic parameters except formation of ascites. In conclusion, CD34 was universally expressed in blood vessels within benign and malignant tissues, whereas CD105 expression was minimal in benign tissues but stronger in gastric carcinoma. These data suggest that both CD105 and CD34 could be used for quantification of angiogenesis, but preference should be given to CD105 in the evaluation of prognosis in gastric carcinoma.     

Hot spot microvessel density and the mitotic activity index are strong additional prognostic indicators in invasive breast cancer

AIMS: Recent studies have drawn attention to intratumoral microvessel density (MVD) as a prognostic factor in invasive breast cancer. Various methods have been applied to assess MVD and the prognostic value of MVD in different studies varies considerably. Counting of microvessels in the most highly vascularized area (hot spot) of a tumour is the method most widely used. In this study we compared three counting methods. METHODS AND RESULTS: To assess MVD in 112 cases of invasive breast cancer with long-term follow-up we performed microvessel counting in the hot spot of the tumour in four and 10 fields of vision (HS-MVD4 and HS-MVD10) and microvessel counting in 10 fields of vision distributed systematically over the whole tumour area (global MVD). The HS-MVD4, HS-MVD10 and global MVD showed good correlations with each other. HS-MVD4 provided the highest number of microvessels (median value 71) followed by HS-MVD10 and global MVD, with median values of 58 and 39, respectively. HS-MVD4 showed the best prognostic value for overall survival (P = 0.0001) whereas HS-MVD10 showed less (P = 0.01) and the global MVD showed no (P = 0.75) prognostic value. In univariate analysis, the HS-MVD4 was the second strongest prognostic factor after tumour size. In multivariate survival analysis, the HS-MVD4, mitotic activity index (MAI), lymph node status and tumour size were found to be independent prognostic factors. When combining MVD4 and MAI in lymph node negative patients, none of the patients with low MVD (< 71/mm2) and a low MAI (< 10 per 10 HPF) died, in contrast to patients with a high MVD or high MAI who have a 10-year survival of 57%. CONCLUSIONS: These data suggest that the hot spot MVD in four fields of vision is a major independent prognostic factor for overall survival in invasive breast cancer. For the first time, it is shown that hot spot MVD provides additional prognostic information to well established factors like lymph node status and the MAI, and may therefore be useful for designing treatment strategies in invasive breast cancer.     

Correlation of microvessel parameters in invasive ductal carcinoma of the breast and fibroadenomas: a morphometric study

Modifications of microvascular configuration are essential features encountered during the progression of breast tumors. Our objectives were to correlate morphometrically evaluated microvessel parameters (microvessel density [MVD], microvessel caliber [VC], microvessel cross-sectional area [VCSA], percentage of total VCSA [%TVCSA], and total microvessel boundary density [TVBD]) with histologic grades of invasive ductal carcinoma (IDC) of the breast and benign breast lesions. Sixty cases of IDC presented with modified radical mastectomy, and 20 benign breast fibroadenomas were evaluated for various microvessel parameters, using CD34-immunostained histologic sections by computerized image morphometry. Samples were divided into 4 histologic groups: benign, grade 1, grade 2, and grade 3; mean with SD and range was evaluated for each group. Histologic grades showed a strong positive correlation with %TVCSA (ρ = 0.773) and TVBD (ρ = 0.811) and a moderate positive correlation with MVD (ρ = 0.607), VC (ρ = 0.609), and VCSA (ρ = 0.616) when analyzed for all samples of the 4 groups. Except MVD, all parameters including age was the lowest (P < .001) for the benign group. Among the IDCs, differences of mean VC and VCSA were not significant; MVD, %TVCSA, and TVBD were the lowest in grade 1 and the highest in grade 3. Upper cutoff value of benign lesions for MVD was 155 mm⁻²; VC, 9.94 μm; VCSA, 94.42 μm²; %TVCSA, 1.33; and TVBD, 4.37 mm⁻¹. Total microvessel boundary density included the information of microvessel concentration and size showed the best correlation with grades. Microvessel density showed a positive correlation with grades in the IDCs, but for the differentiation of benign from malignant, VC, VCSA, %TVCSA, and TVBD showed excellent area under the receiver operating characteristic curve (area under the curve > 0.990), unlike MVD (area under the curve = 0.797).     

乳腺癌中CD105表达及相关因素分析

目的 多项免疫组化（multiple immunohistoehemistry,MIHC）检测内皮因子CD105作为判断患者乳腺癌生物学行为及预后指标的可能性。方法 选取2003年11月-2004年1月经河北医科大学病理科确诊为原发性乳腺癌患者石蜡包埋组织标本87例,癌旁组织标本20例,同期乳腺良性病变标本24例。以CD105单克隆抗体为标记物进行免疫组化染色,根据CD105的表达水平计测微血管密度（mierovessel density,MVD）。结果CD105所标记的MVD在乳腺癌组织和乳腺良性病变以及乳腺良性病变与癌旁组织之间的表达差异均有显著性（P＜0．05）,癌旁组织中CD105几乎表达缺失;淋巴结转移阳性、组织分化差（Ⅲ级）、临床TNM分期晚以及VEGF表达阳性、ER、PR表达阴性的患者中,CD105的表达明显升高,差异均有显著性（P＜0．05）。结论 CD105主要在处于增殖状态的血管内皮细胞上表达,在标记肿瘤组织活性微血管方面特异性极高,是检测乳腺癌患者预后的重要指标。     

Increased microvessel density in malignant and borderline mammary phyllodes tumours

AIMS: Tumour vascularity is considered a prognostic indicator in breast carcinoma, but its utility in mammary phyllodes tumour has not been explored. The authors report the correlation between intratumoral microvessel density and the histological grade of phyllodes tumour. METHODS AND RESULTS: Forty cases of phyllodes tumour were reviewed for stromal cellularity, overgrowth, cytological pleomorphism, mitotic count and margin pattern. Using established criteria, these were diagnosed as benign (n=28), borderline (n=10) and malignant (n=2). Microvessel density was counted on CD31-stained slides as the number of vessels per high power field. For benign phyllodes tumour, the range was 7-26.2 (mean 13.1); for borderline phyllodes tumour the range was 17.2-32.5 (mean 22.4); for malignant phyllodes tumour the range was 25.9-33.3 (mean 29.6). The difference between the benign and borderline groups was significant (P < 0.0001) but that between the borderline and malignant groups was not, due to the small number of malignant cases. CONCLUSIONS: There is a significant difference in stromal microvessel density between benign and borderline phyllodes tumour. Although the small number of cases of malignant phyllodes tumour limits further interpretation, we believe that microvessel density can be used as an additional objective histological parameter in the evaluation of phyllodes tumour.     

The significance of angiogenesis in malignant pheochromocytomas

The purpose of this study was to investigate tumor angiogenesis in a series of benign and malignant pheochromocytomas and to determine whether there is a correlation between angiogenesis and the presence of distant metastases. In this study, the CD31 monoclonal antibody was selected to measure intratumoral microvessel density. Nineteen patients with malignant pheochromocytomas and nineteen patients with benign pheochromocytomas who underwent operation were studied. In order to quantify intratumoral microvessel density, the total number of pixels of CD31-positive reactivity was assessed and expressed as a percentage of the total tissue area in the analyzed field. Analysis of variance revealed a statistically significant correlation between malignancy and intratumoral microvessel density (p=0.0009). Although there was a considerable variability in the intratumoral microvessel density from tumor to tumor within both the benign and the malignant group, a percentage of more than 28.5% anti-CD31 stained area was found only in malignant tumors. In conclusion, this study shows that the mean intratumoral microvessel density in malignant pheochromocytomas is increased approximately two-fold as compared with benign tumors. However, the clinical significance of this prognostic marker is rather weak, because only 4 of the 19 malignant pheochromocytomas had microvesel density higher than this threshold of 28.5%.     

Correlation of intratumoral endothelial cell proliferation with microvessel density (tumor angiogenesis) and tumor cell proliferation in breast carcinoma.

Tumor angiogenesis is essential for tumor growth and metastasis, and intratumoral microvessel density correlates with prognosis in breast carcinoma. Yet, how intratumoral microvessel density correlates with tumor cell and intratumoral endothelial cell proliferation remains incompletely understood. To this end, we stained 57 formalin-fixed, paraffin-embedded breast carcinomas with antibody MIB1 to determine tumor cell Ki67 labeling index and with anti-CD34 to observe microvessels. We correlated the tumor cell Ki67 labeling index and mitotic figure index with intratumoral microvessel density. Using a double labeling technique combining antibody MIB1 and anti-CD34, we measured intratumoral endothelial cell proliferation in 20 of these cases and correlated these findings with tumor cell Ki67 labeling index, mitotic figure index, and intratumoral microvessel density. The intratumoral Ki67-labeling index was 45-fold greater (P < 0.000001) than that of microvessels in adjacent benign breast. Yet, endothelial cell Ki67 labeling index did not correlate with intratumoral microvessel density, tumor cell Ki67 labeling index, or mitotic figure index nor did intratumoral microvessel density correlate with tumor cell Ki67 labeling index or mitotic figure index. These findings suggest that, although endothelial cells are actively proliferating within the tumor, intratumoral microvessel density and intratumoral endothelial cell proliferation are independent of each other and of tumor cell proliferation. Thus, intratumoral microvessel density, endothelial cell proliferation, and tumor cell proliferation may be regulated by separate mechanisms.     

乳腺良恶性肿瘤新生血管超微结构及血管生成相关分子的表达

目的 探讨乳腺良恶性不同肿瘤在新生血管超微结构及其血管生成相关分子表达方面的差异性.方法 应用透射电镜观察乳腺良恶性肿瘤新生血管超微结构改变,免疫组化技术检测CD34、VEGF及其受体Flk-1/KDR在两组肿瘤中的表达特性.结果 恶性组新生血管内皮细胞紧密连接开放,基膜不连续,缺乏平滑肌成分.内皮细胞胞体大,细胞核大,畸形,核仁增大、边集,核质比例增大,胞质内吞饮泡多.较多的单个内皮细胞呈裂隙状,血管腔闭塞或明显狭窄.恶性组MVD高于良性组(P<0.05),微血管丰富区位于痛巢边缘.VEGF在乳腺癌性上皮细胞及癌周血管内皮细胞呈强阳性表达,Flk-1/KDR在乳腺恶性肿瘤m管内皮细胞旱强阳性表达,VEGF及Flk一1/KDR尤其在癌灶边缘呈强阳性表达,良性组几乎不表达(P<0.05).结论 乳腺癌新生血管内皮细胞在超微结构及分子表达上具有异质性,VEGF或受体Flk-1/KDR可能是乳腺癌早期诊断及治疗的分子靶标,癌灶边缘可能是下一步进行乳腺癌分子影像观察的重点靶区.