骨肉瘤肿瘤性粘附因子表达与血管密度及预后的关系

目的：探讨骨肉瘤肿瘤性粘附因子（ＴＡＦ）表达与微血管密度及患者预后关系，方法：应用免疫组化和形态计量方法，检测８０例骨肉瘤ＴＡＦ表达和肿瘤微血管密度，结果：８０例骨肉瘤中３６例ＴＡＦ表达阳性（４０％）阳性反应定位于肿瘤细胞和内皮细胞，以及毛细胞管周围，ＴＡＦ表达与肿瘤微血管密度密切相关（Ｐ〈０．０５），而且ＴＡＦ阳性组生存率显著低于ＴＡＦ阴性组（Ｐ〈０．０５）。结论：ＴＡＦ通过调节血管生成影响骨肉     

乳腺癌组织内微血管定量与转移的关系

肿瘤内微血管定量是反映乳腺癌预后的重要参数。血管计数和密度级别高的乳腺癌易发生转移或复发。微血管定量与乳腺癌浸润周围血管有关。微血管生成除肿瘤源性因素外，还与肿瘤相关的炎性细胞等因素有关。     

肿瘤血管生成与乳腺癌转移及预后的关系

肿瘤血管生成与肿瘤的生长、转移及预后密切相关。通过对乳腺癌组织内微血管的定量计数，发现微血管计数与乳腺癌病人的淋巴结转移、无复发生存率和全部生存率有明显相关性；而且微血管计数与乳腺癌其它一些预后因素及生物学标志也有密切关系。认为乳腺癌组织内微血管的定量计数，可反映肿瘤的血管生成情况，在肿瘤判断预后，筛选高危复发或转移病人、指导治疗等各方面有较大应用价值。     

血管生成与胃癌发展和预后的关系

目的：揭示血管生成与胃癌发展和预后之间的关系。方法：应用免疫组织化学法和抗人因子Ⅷ相关抗原（ＦⅧＲＡｇ）的抗体标记５６例人胃癌组织中的微血管，检测微血管密度（ＭＶＤ），并分析其与胃癌组织学分级、浸润深度、生长方式、淋巴结转移、远处转移和预后的关系。结果：ＭＶＤ与胃癌浸润深度（Ｐ＜０．０１）、淋巴结转移（Ｐ＜０．０１）和远处转移（Ｐ＜０．０５）密切相关，而与组织学分级和生长方式无关（Ｐ＞０．０５）；ＭＶＤ≥４３的胃癌患者５年生存率较低。结论：血管生成对胃癌的发展具有一定作用，ＭＶＤ可成为判断胃癌患者预后的指标之一     

胆管癌对血管和神经周围间隙的侵犯及肿瘤血管生成在浸润和转移中的意义

对４０例胆管癌标本切片进行血管内膜下弹力纤维ＶＢ：ＨＥ、ＦⅧＲＡｇ：ＶＢ：Ｈ及ＨＥ染色，结果显示，血管侵犯者３１例（７７．５％），表现为４种类型，即血管壁受侵、游离癌细胞侵入、部分栓塞和完全栓塞。肿瘤血管密度（ＴＶＤ）与转移发生明显相关。发生神经周围间隙浸润者共３３例（８２．５％），神经周围浸润指数（ＰＮＩ）与器官或组织转移发生率相关。研究表明，血管和神经周围间隙均是重要的转移途径。肿瘤血管生成是浸润、转移发生必不可少的环节。ＴＶＤ和ＰＮＩ对于判断患者术后预后具有一定的参考意义。     

小鼠S180移植瘤血管生成作用及其调节机制的研究

目的：观察肉瘤180(S180)移植瘤发展过程中血管生成及血管生成调节因子的变化,并对其调节机制进行探讨。 方法： 利用Km小鼠的S180移植瘤模型，采用FⅧ因子免疫组化染色检测肿瘤血管生成，ELISA和EIA法检测荷瘤鼠肿瘤组织和血浆中血管内皮生长因子（VEGF）和内皮抑制素（endostatin）水平，采用多元回归分析肿瘤组织微血管计数、血管形态与瘤重变化的关系。 结果： 随着荷瘤时间延长，肿瘤组织内微血管计数，瘤内血管相对总量增加，血管的相对面积增大（P<0.05）；肿瘤组织匀浆中VEGF水平在荷瘤10 d、15 d均显著高于5 d组（P<0.05）；endostatin在肿瘤匀浆和血浆中均在荷瘤15 d达到最高（P<0.05）；V/E比值无显著变化；微血管计数、血管相对总面积与瘤重变化有相关性（P<0.01）。 结论： S180移植瘤病期发展中微血管数目增加，血管口径增大，且与瘤重变化呈正相关；肿瘤发展过程中肿瘤局部血管生成正调节因子逐渐增加，促进血管生成；肿瘤局部血管生成调节因子处于相对的平衡。     

血管内皮细胞生长因子和血管生成与胃癌发展的关系

目的探讨血管内皮细胞生长因子（ＶＥＧＦ）和血管生成与胃癌发展的关系。方法应用免疫组织化学和原位分子杂交技术,检测５６例人胃癌组织ＶＥＧＦ蛋白表达和微血管密度（ＭＶＤ）及部分胃癌ＶＥＧＦｍＲＮＡ表达,分析ＶＥＧＦ和ＭＶＤ、及其与胃癌组织学分型、浸润深度、生长方式、淋巴结转移、远处转移和预后的关系。结果ＶＥＧＦ阳性者ＭＶＤ值显著高于阴性者（Ｐ＜００１）,ＶＥＧＦ表达和ＭＶＤ与胃癌浸润深度（Ｐ＜００１）、淋巴结转移（Ｐ＜００５）和远处转移（Ｐ＜０．０５）密切相关,而与组织学分型和生长方式无关（Ｐ＞００５）;ＶＥＧＦ表达阳性或ＭＶＤ≥４３的胃癌患者５年生存率较低;ＶＥＧＦｍＲＮＡ表达与ＶＥＧＦ蛋白表达具有一致性,但其分布不同。结论ＶＥＧＦ与胃癌的血管生成密切相关,对胃癌的生长和浸润转移有促进作用,ＶＥＧＦ和ＭＶＤ可作为反映胃癌生物学行为的指标之一     

乳腺癌层粘连蛋白受体表达与微血管密度和转移及复 …

目的：探讨乳腺癌层粘连蛋白受体（ＬＮ－Ｒ）与间质微血管密度和肿瘤转移、复发的关系及意义。方法：应用免疫组化ＬＳＡＢ法检测７３例乳腺癌ＬＮ－Ｒ,ＦⅧＡｇ的表达,并对２８例病人进行随访分析。结果：ＬＮ－Ｒ的表达程度与乳腺癌淋巴结转移存在正相关（Ｐ〈０．０００１）,与病理分级无关（Ｐ〉０．０５）,与乳腺癌间质微血管密度（ＭＶＤ）存在正相关（Ｐ〈０．０００１）。淋巴结转移阳性组其ＭＶＤ值明显高于阴性组（Ｐ     

骨肉瘤中Wnt5a表达及其与血管生成的关系

目的探讨Wnt5a在骨肉瘤组织中的表达及其与血管生成的关系。方法采用免疫组化法检测45例骨肉瘤组织及15例骨软骨瘤组织中Wnt5a和CD34的表达,根据CD34染色结果进行微血管密度(microvessel density,MVD)计数,并分析Wnt5a表达和MVD计数与骨肉瘤患者临床病理特征及预后的关系。结果骨肉瘤组织中Wnt5a和CD34表达(阳性率分别为60. 0%和71. 1%)明显高于骨软骨瘤(阳性率分别为13. 3%和20. 0%)(P均0. 05)。在骨肉瘤中,Wnt5a表达和MVD计数与Enneking分期和远处转移密切相关(P均0. 05),与患者性别、年龄、肿瘤部位、组织学类型等无关。Spearman相关分析表明,Wnt5a蛋白表达与MVD计数呈正相关(r=0. 380,P=0. 010)。Kaplan-Meier生存分析发现,Wnt5a和MVD阳性患者的生存时间明显短于阴性患者(P均0. 05)。结论骨肉瘤中Wnt5a呈高表达,可能与肿瘤血管生成相关,Wnt5a有望成为骨肉瘤抗血管生成治疗中新靶向分子。     

广东汉族人类风湿关节炎易感性与HLA-DRB1基因相关性研究

目的探讨ＨＬＡ－ＤＲＢ１基因与类风湿关节炎（ＲＡ）相关性。方法采用ＰＣＲ－ＳＳＰ方法对４７例广东汉族人ＲＡ患者进行ＨＬＡ－ＤＲＢ１基因分型，并与相应人群健康者１０２例结果比较。结果ＨＬＡ－ＤＲ４基因在ＲＡ组显著增高（３５．１％，ＲＲ＝３．５５，Ｐ＜０．００５，ＥＦ＝０．２５２），ＤＲ１６在ＲＡ组也高于正常（ＲＲ＝２．５７，Ｐ＜０．０５）；而ＤＲ９基因在ＲＡ组显著减少（Ｐ＜０．００５）。３１例ＤＲ４＋患者患病年龄较早，病情较重（类风湿因子阳性率和Ⅱ期ＲＡ骨关节Ｘ线改变者显著高于ＤＲ４－患者，Ｐ值分别＜０．０５和０．０２５）。结论广东汉族人ＲＡ易感性与宿主ＤＲ４基因密切相关，ＨＬＡ－ＤＲ４可能是一个对判断病情和预后有价值的实验指标。     

Tumor angiogenesis in advanced stage ovarian carcinoma.

Tumor angiogenesis has been found to have prognostic significance in many tumor types for predicting an increased risk of metastasis. We assessed tumor vascularity in 43 cases of advanced stage (International Federation of Gynecologists and Obstetricians stages III and IV) ovarian cancer by using the highly specific endothelial cell marker CD34. Microvessel counts and stage were associated with disease-free survival and with overall survival by Kaplan-Meier analysis. The plots show that higher stage, higher average vessel count at 200x (200x avg) and 400x (400x avg) magnification and highest vessel count at 400x (400x high) magnification confer a worse prognosis for disease-free survival. Average vessel count of less than 16 (400x avg, P2 = 0.01) and less than 45 (200x avg, P2 = 0.026) suggested a better survival. Similarly, a high vessel count of less than 20 (400x high, P2 = 0.019) conferred a better survival as well. The plots suggest that higher stage, higher average vessel count at 200x and 400x, and highest vessel count at 200x and 400x show a trend to worse overall survival as well. With the Cox proportional hazards model, stage was the best predictor of overall survival, however, the average microvessel count at 400x was found to be the best predictor of disease-free survival. These results suggest that analysis of neovascularization in advanced stage ovarian cancer may be a useful prognostic factor.     

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.     

Prognostic role of microvessel density in patients with renal cell carcinoma: a meta-analysis

Microvessel density (MVD), an indicator of angiogenesis, has been proposed to predict prognosis of patients with renal cell carcinoma (RCC), but its ability to predict survival of patients with RCC remains controversial. The present study sought to address this question rigorously by systematically reviewing the literature on MVD and RCC prognosis. We identified relevant studies in PubMed, EMBASE and the Cochrane Library, and two reviewers independently assessed study quality and extracted relevant data to compare survival based on MVD stratification in patients with RCC. We identified 15 studies that satisfied the inclusion criteria; eight studies assessed MVD in surgical samples by immunohistochemistry to label factor VIII; four studies, by immunohistochemistry to label CD34; two studies, CD31; and one study, CD105. Survival meta-analysis was performed using data pooled from 10 studies: five based on factor VIII, two based on CD34, two based on CD31 and one based on CD105. The overall survival hazard ratio describing the relationship between MVD and survival in all 10 pooled studies was 0.964 (95% CI: 0.873-1.065), while the individual hazard ratios for pooled studies based on factor VIII were 1.673 (95% CI: 0.860-3.252); CD34, 0.903 (95% CI: 0.853-0.956); and CD31, 0.926 (95% CI: 0.868-0.989). The corresponding result for the sole trial based on CD105 was 0.1759 (95% CI: 0.036-0.856). These findings suggest that MVD is not reliably associated with survival time of patients with RCC, which may reflect the need to take into account whether the microvasculature is differentiated or not. MVD as currently calculated may not be an ideal prognostic factor for patients with RCC.     

The prognostic relevance of angiogenesis and mast cells in squamous cell carcinoma of the oesophagus

AIMS: Angiogenesis, an important prognostic factor in several tumours, is a complex event mediated by angiogenic factors released from cancer cells and host immune cells. Among the host immune cells, a role has been implicated for mast cells in tumour progression via promoting angiogenesis. Data have been recorded that indicate a correlation between intratumoral neovascularisation, as assessed by microvessel density (MVD), and prognosis in squamous cell carcinoma (SCC) of the oesophagus. However, a correlation between mast cell density (MCD) and either prognosis or angiogenesis has not been delineated yet in this disease. The aim of this study was to investigate the prognostic value of MVD and MCD in SCC of the oesophagus. The correlation between MVD and MCD was also evaluated. METHODS: MVD and MCD were investigated in tumour specimens from 53 patients diagnosed with SCC of the oesophagus. Intratumoral microvessels were stained with anti-CD34 antibody and mast cells with toluidine blue before being measured by light microscopy. RESULTS: Both MVD and MCD were associated with the depth of wall invasion, lymph node metastasis, and tumour progression (stage). A significant correlation was noted between MVD and MCD values (r = 0.72). The prognosis was significantly worse in patients with high MVD (> or = 92) and high MCD (> or = 18) values. Multivariate analysis indicated that MVD and stage were independent predictors of survival. CONCLUSIONS: These findings support the suggestion that MVD is a reliable prognostic marker in SCC of the oesophagus. Moreover, MCD may have a role in the angiogenesis of these tumours and might be responsible for their aggressive behaviour.     

Vitronectin significantly influences prognosis in osteosarcoma

Vitronectin (Vn), a multifunctional adhesive protein, is found in association with tumor progression, angiogenesis and metastasis in a variety of (human) tumors. But no studies concerning its correlation to osteosarcoma prognosis were found. Hence, we aimed to investigate the prognostic value of Vitronectin (Vn) in osteosarcoma. Here, we studied the expression of VN in the tumor tissues from 67 patients with osteosarcoma and 20 patients with osteochondroma using immunohistochemistry and estimated the effects of VN expression in osteosarcoma on progression-free survival (PFS) and overall survival (OS) using the Kaplan-Meier curve and COX proportional hazards regression model. Increased expression of VN in osteosarcoma tissue compared to no VN expression in osteochondroma tissue was shown in immunohistochemical assay. No associations were observed between VN expression and osteosarcoma patients’ gender (P = 0.675), age (P = 0.813), tumor size (P = 0.436), histologic subtype (P = 0.0.543) or tumor location (P = 0.456). Univariate survival analysis demonstrated significant correlations of high VN expression with shorter PFS (P = 0.002) and OS (P = 0.001); multivariate survival analysis revealed high VN expression as a significant independent prognostic indicator for shorter PFS (HR 2.788, P = 0.003) and OS (HR2.817, P = 0.003). In conclusion, the high expression of VN in tumor cells independently indicated poor clinical prognosis in patients with osteosarcoma, other than large tumor size and non-neoadjuvant chemoradiotherapy, suggesting that VN may serve as a potential therapeutic target in osteosarcoma.     

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。     

Angiogenesis relates to estrogen receptor negativity,c-erbB-2 overexpression and early relapse in node-negative ductal carcinoma of the breast

Tumor angiogenic activity is an important process linked to tumor growth, metastasis, and invasion. In the present study we investigated whether intratumoral microvessel density (MVD), as assessed with immunohistochemistry, is of prognostic relevance in a series of 77 breast cancer patients with node-negative disease. The mean MVD in the hot spots ranged from 9 to 106 (median 31) vessels per x200 optical field. Patients were grouped into 3 categories of low (27 pts), medium (26 pts), and high (24 pts) MVD. Angiogenesis was not related to the primary tumor dimensions (T-stage) or the histology differentiation. An inverse association of MVD with estrogen receptor (ER) expression was noted (p=0.0007), while high MVD was directly related to c-erbB-2 overexpression (p=0.04) and high MIB1 proliferation index (p=0.02). In univariate and multivariate analysis of relapse-free survival, MVD was the only variable significantly and independently linked to relapse. It is concluded that high intratumoral angiogenic activity is linked with early relapse in node-negative breast cancer.     

A study of proliferative activity, angiogenesis and nuclear grading in renal cell carcinoma

To evaluate the role of proliferative marker, proliferating cell nuclear antigen (PCNA) and microvessel density (MVD) as prognostic markers in renal cell carcinoma (RCC) and to see their relationship with the clinical stage and nuclear grades, we studied 30 cases of RCC for nuclear grading (Fuhrman's nuclear grade), MVD (using anti CD-34 antibody), and PCNA labeling index (using anti-PCNA antibody) over a period of 2.5 years. Staging was assessed by peroperative and radiologic findings. The area of highest MVD within the tumor was selected for microvessel count (MVC) per high-power field (0.1885 mm 2 area). PCNA labeling index was determined by counting percentage of positively stained tumor cell nuclei. PCNA labeling index above 60% was taken as high PCNA index and up to 60% was considered low. There was significant positive correlation between PCNA labeling index with both nuclear grade and clinical stage using Spearman's correlation coefficient. No association was noted between MVC with PCNA, nuclear grade, and clinical stages. Evaluation of proliferative status of RCC is a useful adjunct as a prognostic parameter as it is seen to correlate well with both clinical stage and nuclear grade. In our study, MVD was not seen to correlate with either of these.