食管鳞癌p53、TSP-1、VEGF表达与肿瘤血管生成

目的 探讨食管鳞癌中p53、血小板反应蛋白-1（TSP-1）和血管内皮生长因子（VEGF）的表达与肿瘤血管生成的关系。方法 利用免疫组织化学（SP法）方法检测68例食管鳞癌组织中p53、TSP-1和VEGF的表达及肿瘤内微血管密度（MVD）计数。结果 食管鳞癌组织中p53、TSP-1、VEGF阳性率分别为72.06%、29.41%和64.71%。p53与TSP-1呈负相关（rs =－1.000,P〈0.01）,与VEGF呈正相关（rs =1.000,P〈0.01）。TSP-1阳性组MVD为18.37±4.86,TSP-1阴性组MVD为29.80±6.35（t = 2.735,P〈0.01）,TSP-1与MVD呈负相关（rs =－0.783,P〈0.01）。结论 p53通过调节TSP-1和VEGF的表达,促进了食管鳞癌组织新生血管的生成。     

Angiopoietin 2 expression in invasive ductal carcinoma of the breast: its relationship to the VEGF expression and microvessel density

Summary Angiopoietin (Ang) is a ligand for the endothelium-specific tyrosine kinase receptor Tie-2, while a shift in the Ang-1:Ang-2 expression ratio in favor of Ang-2 was found to be associated with tumor angiogenesis. In the present study, we analyzed the immunohistochemical expression of Ang-2 in a series of 198 breast cancers, in which VEGF expression and microvessel density (MVD) were previously determined. Ang-2 expression was negative in 24 (12%), positive in 50 (25%) and strongly positive in 124 (63%) of 198 cases. A significant correlation was found between Ang-2 and VEGF expressions (p=0.0004) and between Ang-2 expression and MVD (p=0.0006), while a high MVD was found in 10 (77%) of 13 tumors with a strongly positive VEGF and positive Ang-2 expression and in 40 (71%) of 56 tumors with a strongly positive VEGF and strongly positive Ang-2 expression. Although there was no difference in the disease free survival (DFS) stratified according to Ang-2 expression alone, the 69 patients with a strongly positive VEGF and a strongly positive or positive Ang-2 expression had a significantly (p=0.0316) worse DFS than those with other combinations of VEGF and Ang-2 expressions. A multivariate analysis indicated lymph node metastasis and MVD to be independently significant prognostic factors for DFS, while the combination of VEGF and Ang-2 expressions was not a significant factor for DFS. In conclusion, the Ang-2 expression was found to be closely correlated with VEGF expression and MVD in breast cancer, while a high MVD was frequently found in tumors with a high expression of both VEGF and Ang-2. The survival analysis demonstrated a high MVD, which was induced by a high expression of both VEGF and Ang-2, to therefore have a strong prognostic significance in breast cancer.     

血管内皮生长因子、血管生成素在食管鳞状细胞癌组织中的表达及其意义

目的 研究血管内皮生长因子(VEGF)、血管生成素(Ang)-1及Ang-2在食管鳞状细胞癌(ESCC)中的表达及其与预后的关系.方法 用免疫组织化学二步法检测60份ESCC、20份食管癌旁组织及10份正常食管黏膜上皮组织中VEGF、Ang-1及Ang-2的表达,计数微血管密度(MVD).结果 ESCC与食管癌旁组织及食管正常鳞状上皮组织比较,Ang-1表达率显著降低,而VEGF及Ang-2表达率则显著升高(P＜0.05).MVD在Ang-1阴性表达组显著高于阳性表达组(P=0.000);MVD在VEGF、Ang-2阳性表达组显著高于阴性表达组(P＜0.05).Ang-1表达与肿瘤分化程度显著相关(P=0.013).T3、T4期VEGF和Ang-2表达率显著高于T1、T2期(P＜0.05);VEGF及Ang-2在有淋巴结转移者显著高于无淋巴结转移者(P＜0.001).VEGF及Ang-2表达阳性组术后3年生存率低于阴性表达组(P＜0.05),Ang-1表达阳性和阴性组比较,差异无统计学意义(P=0.749).结论 Ang-1表达的降低及Ang-2、VEGF表达的增高可能与食管癌的发生、发展密切相关;VEGF及Ang-2在食管癌中表达提示预后不良.     

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     

Clinical significance of thrombospondin-1 expression in relation to vascular endothelial growth factor and interleukin-10 expression at the deepest invasive tumor site of advanced colorectal carcinoma

Various angiogenic and angiostatic factors regulate angiogenesis. Tumor angiogenesis is a complicated process for which the detailed mechanisms remain unclear. The aim of this study was to elucidate the clinical significance of TSP-1 expression in relation to expression of VEGF and IL-10 and angiogenesis at the deepest invasive tumor site as a predictor of invasive/metastatic potential and prognosis of advanced colorectal carcinoma (CRC). Patients (n=152) who had undergone surgical resection for advanced CRC were entered in this study. Expression of TSP-1, VEGF, and IL-10 was examined immunohistochemically with specific antibodies. Tumor microvessel density (MVD) was also determined immunohistochemically with anti-CD34 antibody (NU-4A1). Expression of TSP-1, VEGF, and IL-10 at the deepest invasive tumor site was detected in 46 (30.3%), 62 (40.8%), and 39 (25.7%) of 152 lesions, respectively. TSP-1, VEGF, and IL-10 expression at the superficial part was detected in 60 (39.5%), 35 (23.0%), and 46 (30.3%) of 152 lesions, respectively. Although there was no significant difference between the incidence of TSP-1 and IL-10 expression at the deepest invasive site or at the superficial part, there was a significant difference between the incidence of VEGF expression at the deepest invasive site and that at the superficial part. Expression of TSP-1 and IL-10 at the deepest invasive tumor site was inversely correlated with metastatic potential and prognosis in relation to MVD. Furthermore, lesions that were TSP-1-negative and VEGF-positive at the deepest invasive tumor site showed the strongest association with MVD. The 5-year survival rate for patients with TSP-1-negative or IL-10 negative lesions at the deepest invasive tumor site was significantly poorer than that for patients with TSP-1-positive or IL-10-positive lesions, respectively. The 5-year survival rate for patients with VEGF expression at the deepest invasive tumor site was significantly poorer than that for patients without VEGF expression. The 5-year survival rate for patients with TSP-1-negative, VEGF-positive lesions at the deepest invasive site were significantly poorer than that for patients with lesions without these characteristics. Multivariate analysis with logistic regression for 5-year survival in patients with curative surgery showed that lymph node metastasis and VEGF expression were significant prognostic factors. Although lack of TSP-1 or IL-10 expression was associated significantly with poorer prognosis, this may be less important in poorer prognosis than the presence of VEGF expression.     

The angiogenic and prognostic implications of VEGF, Ang-1, Ang-2, and MMP-9 for hepatocellular carcinoma with background of hepatitis B virus

The objective of this study was to investigate the expressions of angiogenic factors and elucidate their angiogenic and prognostic roles in hepatocellular carcinoma (HCC) with background of hepatitis B virus (HBV). We evaluated microvessel density (MVD) of HCC, and investigated immunohistochemical expression of vascular endothelial growth factor (VEGF), angiopoietins (Ang-1 and Ang-2), and matrix metalloproteinases-9 (MMP-9) in 67 specimens of surgically resected HCC, which were all positive for hepatitis B surface antigen. We investigated the relationship between their expressions and clinicopathological factors or prognosis. The microvessel density (MVD) of tumor tissue and surrounding normal liver tissue was 93.1 ± 43.8/mm² and 30.4 ± 14.8/mm², respectively. The MVD of well-differentiated HCC was significantly less than that of poorly differentiated HCC. MVD was positively correlated with VEGF and Ang-2 expression (P = 0.0023 and 0.0265, respectively). There was less tumor recurrence in low Ang-2 and low MMP-9 group than high Ang-2 and/or high MMP-9 group (P = 0.002). In Cox regression model, portal vein thrombus and intrahepatic metastasis was the risk factors of tumor recurrence (P = 0.003 and 0.001, respectively). Our study showed that the expression of VEGF and Ang-2 were positively correlated with MVD. Ang-2 expression and/or MMP-9 expression might be a significant predictive factor for recurrence after resection in HCC patients with the background of HBV.     

Expression and prognostic significance of angiopoietin in colorectal carcinoma

BACKGROUND AND OBJECTIVES: Growth and metastasis of malignant tumors depend on the angiogenesis. The aim of this study was to elucidate the prognostic significance of angiopoietin-1 (Ang-1) and angiopoietin-2 (Ang-2) expression in advanced colorectal carcinoma. METHODS: Totally, 101 patients with surgically resected advanced colorectal carcinomas were enrolled. The tumor expressions of Ang-1 and Ang-2 were evaluated immunohistochemically, and their relationships with clinicopathological factors and prognosis were investigated. Tumor microvessel density (MVD) was also calculated and correlated with angiopoietin expression. RESULTS: Ang-1 and Ang-2 were detected in 26 (25.7%) and 45 (44.6%), respectively, of 101 cancerous lesions. Overexpression of Ang-1 was correlated with high MVD. Overexpression of Ang-2 was correlated with lymph node metastasis, venous invasion, preoperative carcinoembryonic antigen levels, and high MVD (P < or = 0.05). MVD was not significantly upregulated by Ang-1 expression, but was significantly upregulated by Ang-2 expression (P < or = 0.01). However, only patients with Ang-2 overexpression showed a significantly worse prognosis than those without Ang-2 overexpression. Multivariate analysis with logistic regression for 5-year survival revealed that cancerous stage and Ang-2 overexpression were independent prognostic indicators. CONCLUSIONS: The Ang-1 expression correlated with MVD. However, Ang-2 expression was a useful prognostic marker in the management of patients with advanced colorectal carcinoma.     

Thrombospondin-1 expression in oral squamous cell carcinomas: correlations with tumor vascularity, clinicopathological features and survival

Thrombospondin-1 (TSP-1) is a 450 kd glycoprotein synthesized and incorporated into the extracellular matrix by numerous cell types and reported to suppress tumor growth and progression by its inhibition of angiogenesis. In order to clarify the biological role of TSP-1 and determine its clinicopathological significance in oral squamous cell carcinomas (SCCs), we identified TSP-1 protein expression in 54 oral SCCs by immunohistochemistry and correlated it with microvessel density (MVD), clinicopathological features and patient's survival. Thirty-two out of 54 carcinomas (59%) were identified as having a low level of TSP-1 expression (TSP-1-L), and 22/54 (41%) carcinomas identified as having a high level of TSP-1 expression (TSP-1-H). The MVD counts (mean±S.D.=9.0±4.9) in TSP-1-H tumors was significantly lower than that (mean±S.D.=12.7±4.4) in TSP-1-H tumors (P=0.0065). The level of TSP-1 expression was not correlated with T category and histologic grade, but inversely correlated with the pattern of tumor invasion (P=0.0136) and with lymph nodal status (P=0.0119). Furthermore, Kaplan–Meier analysis showed that the 5-year survival rate of TSP-1-H group was significantly higher than that of TSP-l-L group. Our results suggested that TSP-1 expression exerts an inhibitory effect on tumor vascularity, and that it has value in assessment of aggressiveness and prognosis of oral SCCs.     

Angiopoietin-2和VEGF在口腔鳞癌中的表达及意义

目的研究口腔鳞癌组织中Ang-2和VEGF的表达并分析它们与肿瘤临床病理学特征和血管生成及血管成熟间的关系。方法:用常规的免疫组织化学的方法检测41例口腔鳞癌及30例癌旁正常组织和10例正常口腔黏膜中的Ang-2及VEGF的表达;通过双标免疫组织化学法同时染CD34(标记所有血管内皮细胞)和α-平滑肌肌动蛋白(标记血管壁细胞包括血管平滑肌细胞和周细胞)评估微血管密度(MVD)及血管成熟指数(VMI)。结果在口腔鳞癌组织中Ang-2和VEGF的阳性表达率分别为21(51.22%)和26(63.42%);Ang-2和VEGF在口腔鳞癌组织中表达显著高于它们在癌旁正常组织(P<0.05)和正常口腔黏膜组织中的表达(P<0.05);Ang-2表达与肿瘤的淋巴结转移密切相关(P<0.01)而VEGF表达与肿瘤的肿瘤分化程度相关(P<0.05),它们与病人的性别、年龄及TNM分期无关(P>0.05);Ang-2和VEGF表达阳性的鳞癌组织MVD显著高于它们阴性表达组(P<0.05)而Ang-2表达阳性的鳞癌组织VMI显著低于Ang-2表达阴性组(P<0.05)。在联合VEGF表达的情况下,同时表达Ang-2和VEGF的肿瘤MVD(51.08±2.99)显著高于其他任何表达状况(P<0.05)。结论Ang-2和VEGF在口腔鳞癌组织中的过表达可能在口腔鳞癌的进展过程中起重要作用;它们与肿瘤的血管生成和成熟密切有关。     

促血管生成素-2对胃癌血管生成的双向效应

目的　探讨促血管生成素 2 (Ang 2 )在胃癌血管生成中的作用。方法　运用RT PCR和S P免疫组化方法检测Ang 2mRNA、血管内皮生长因子 (VEGF)、CD34蛋白在 36例胃癌及其相应癌旁胃黏膜组织中的表达。结果　胃癌组织及其相应癌旁胃黏膜组织均见有Ang 2mRNA阳性表达 ,胃癌组织Ang 2mRNA的总体表达水平与微血管密度 (MVD)未见明显相关。胃癌组织Ang 2mRNA表达水平低于癌旁胃黏膜组织者 2 7例 ,其癌组织中 ,Ang 2mRNA的表达水平与MVD呈正相关 (r=0 .4 11,P <0 .0 5 ) ;同时 ,VEGF阳性表达者的MVD(45 .4 5± 10 .30 )明显高于VEGF阴性染色者 (30 .15± 8.6 9,P <0 .0 5 ) ,即在Ang 2表达上调的情况下VEGF促进血管生成。胃癌组织Ang 2mRNA表达水平高于癌旁组织者 9例 ,其癌组织中Ang 2mRNA的表达水平与肿瘤组织的MVD呈负相关 (r =- 0 .75 8,P <0 .0 5 ) ,VEGF的阳性表达者与阴性染色者间 ,MVD差异无显著性 ,即Ang 2抑制血管生成与VEGF的表达无相关性。结论　Ang 2对胃癌血管生成具有双向调节作用。     

Clinical significance of angiopoietin-2 expression at the deepest invasive tumor site of advanced colorectal carcinoma

Angiopoietin (Ang)-2 and vascular endothelial growth factor (VEGF) are thought to be critical regulators in tumor angiogenesis. We investigated the clinical significance of Ang-2 expression at the deepest invasive tumor site under the influence of VEGF expression in relation to angiogenesis, invasive/metastatic potential, and prognosis of advanced colorectal carcinoma (CRC). One hundred and fifty-two patients who underwent surgical resection for advanced CRC were enrolled in this study. Ang-2 and VEGF expression were examined immunohistochemically. Tumor microvessel density (MVD) was examined by immunohistochemical staining against CD34. Ang-2 and VEGF were expressed at the deepest invasive tumor site in 90 (59.2%) and 64 (42.1%) of 152 lesions, respectively. Patients with Ang-2 expression at the deepest invasive tumor site showed significantly (p<0.01) more frequent poorly histologic grade (71.9%), lymphatic involvement (65.9%), venous involvement (69.1%), lymph node metastasis (75.0%), liver metastasis (80.0%) and advanced disease (Dukes' stage C, 70.2%; stage D, 80.0%) than patients without Ang-2 expression. MVD was not significantly up-regulated by Ang-2 expression alone at the deepest invasive tumor site but was significantly up-regulated by VEGF expression at the deepest invasive tumor site under the positive-Ang-2 condition. In patients treated by curative surgery, patients with tumors showing both positive-Ang-2 and positive-VEGF condition at the deepest invasive tumor site had significantly poorer prognoses than patients with tumors under other conditions. Multivariate analysis with logistic regression for 5-year survival in cases of curative surgery showed that lymph node metastasis, VEGF expression and Ang-2 expression were significant factors to predict poor prognosis. Our results suggest that Ang-2 expression in collaboration with VEGF expression at the deepest invasive tumor site may result in tumor angiogenesis and that these angiogenic factors at the deepest invasive tumor site may be correlated with invasive/malignant potential and prognosis of advanced CRC.     

Significance of tumour-associated macrophages, vascular endothelial growth factor and thrombospondin-1 expression for tumour angiogenesis and prognosis in endometrial carcinomas.

Angiogenesis is a key process in tumour growth and metastasis, and microvessel density has been found to influence the prognosis of endometrial carcinoma patients. Less is known about regulators of angiogenesis. Studies of other tumour types have indicated that the density of tumour-associated macrophages (TAMs) and the expression of vascular endothelial growth factor (VEGF) might stimulate vessel formation, whereas thrombospondin-1 (TSP-1) may inhibit this process. We investigated the influence of TAM (CD68+), VEGF and TSP-1 expression on tumour vascular density and prognosis among endometrial carcinoma patients and compared our findings with clinico-pathological variables and tumour markers. In a prospective study, 60 endometrial carcinoma patients with long (median 11 years) and complete follow-up were included. Intratumour density of TAMs was significantly associated with FIGO stage, histological type, histological grade, DNA index, estradiol receptor concentration, intratumour Ki-67 and p53 protein expression (all p < 0.05). Moderate or strong expression of VEGF was significantly associated with serous papillary/clear cell tumour types, high microvessel density and aneuploidy (p < 0.05). There was a tendency to strong TSP-1 expression among tumours with weak VEGF expression (p=0.09). TAM density influenced survival significantly in univariate survival analysis (Kaplan-Meier method, p<0.05) in contrast to VEGF and TSP-1 expression. In Cox regression analysis, however, no independent prognostic impact remained. In conclusion, moderate or strong VEGF expression was significantly associated with high microvessel density and TAM count was increased in a subgroup of aggressive tumours. High TAM density was significantly associated with reduced survival in univariate analysis.     

Ang-2、VEGF及VEGFR3在喉鳞癌中的表达及其临床意义

 目的 研究喉鳞癌组织中促血管生成素-2(Angiopoietin-2,Ang-2)、血管内皮生长因子（vascular endothelial growth factor,VEGF）及受体-3（VEGFR-3）的表达及其与临床病理学特征间的关系。 方法 采用免疫组织化学方法检测喉鳞癌患者癌组织及癌旁正常组织中促血管生成素-2（Ang 2）、血管内皮生长因子（VEGF）及血管内皮生长因子受体-3（VEGFR-3）的表达。 结果 Ang-2、VEGF及VEGFR-3在喉鳞癌组织中表达显著高于癌旁正常组织（P均<0.01）;Ang-2表达在肿瘤病理分化程度及有无淋巴结转移上差异无统计学意义（P>0.05）, VEGF与VEGFR 3的表达在病理分化程度上的比较差异无统计学意义（P>0.05）,而有无淋巴结转移上的比较差异有统计学意义（P<0.05）; Pearson积差相关性分析：喉鳞癌组织中Ang-2与VEGF的表达呈正相关（r=0.8193,P<0.01）;VEGF与VEGFR-3的表达也呈正相关（r=0.7365,P<0.01）。 结论 Ang-2、VEGF及VEGFR-3与肿瘤的血管生成和成熟密切相关,它们在喉鳞癌组织中的过表达可能在喉鳞癌的发展过程中起重要作用。     

Ang-1和Ang-2在肝细胞癌组织中的表达及其与血管生成的关系

目的 探讨Ang-1和Ang-2在肝细胞癌(HCC)组织中的表达及其与肿瘤血管生成的关系.方法 使用免疫组化法检测36例HCC组织和5例正常肝组织中,Ang-1和Ang-2的表达,检测HCC组织的微血管密度(MVD).结果 5例正常肝组织中,Ang-1阳性者3例,Ang-2均为阴性.HCC组织中Ang-2阳性率为83.33％,明显高于癌旁组织的33.33％ (P ＜0.05).Ang-2表达与MVD有关,Ang-2阳性者MVD为28.48±10.36,阴性者为14.22±11.02,差异有统计学意义(P＜0.05).Ang-2表达与血管侵犯、侵袭转移程度有关(P＜0.05).结论 HCC组织中Ang-2高表达,且与肿瘤血管生成有关,检测Ang-2有助于判断肿瘤侵袭转移能力,但不能反映恶性程度.     

非小细胞肺癌患者血清中VEGF和Ang-2的表达和临床意义

目的:检测非小细胞肺癌（NSCLC）患者血清中血管内皮生长因子（VEGF）和血管生成素-2（Ang-2）的含量,探讨血清中VEGF和Ang-2与肿瘤血管生成的关系及其临床意义。方法:收集40例NSCLC患者血清和肿瘤组织,以40例健康志愿者血清为对照,采用ELISA方法检测血清中VEGF和Ang-2的含量,应用免疫组化法检测肿瘤组织中的微血管密度（MVD）,分析血清中VEGF和Ang-2与肿瘤血管生成、临床病理资料和预后的相关性。结果:NSCLC患者血清中VEGF［（625.6±312.5）pg/ml］和Ang-2［（2450.2±1021.1）pg/ml］的含量明显高于正常对照组血清中VEGF［（321.4±102.6）pg/ml］和Ang-2［（1020.6±421.6）pg/ml］的含量（P<0.05）。NSCLC患者血清中VEGF和Ang-2的含量均与肿瘤的MVD呈正相关(r=0．525,P<0.01;r=0．612,P<0.01)。NSCLC患者血清中VEGF和Ang-2的含量与肿瘤大小、淋巴结转移及临床分期有关（P<0.05）。血清中VEGF和Ang-2高表达的患者总生存时间明显低于低表达患者（P<0.05）。结论:VEGF和Ang-2 在NSCLC的血管生成和发展中发挥重要作用,两者可作为NSCLC诊断和预后判断的潜在的分子标志物。     

胃癌组织中Ａｎｇ ２和ＶＥＧＦ的表达与血管生成的关系

目的：研究胃癌组织中血管生成素-２（Ａｎｇ-２）和血管内皮生长因子（ＶＥＧＦ）的表达与临床病理学特征和肿瘤血管生成的关系。方法：应用免疫组织化学方法检测５５例胃癌组织以及１２例胃癌癌旁组织和正常胃组织中Ａｎｇ-２、ＶＥＧＦ表达及微血管密度（ＭＶＤ）。结果：Ａｎｇ-２、ＶＥＧＦ表达及ＭＶＤ在胃癌组织中均显著高于癌旁组织及正常胃组织（Ｐ＜０.０５）;胃癌组织Ａｎｇ-２、ＶＥＧＦ表达与浸润深度、淋巴结转移、病理分期、肿瘤分化程度密切相关（Ｐ＜０.０５）;Ａｎｇ-２与ＶＥＧＦ表达呈正相关性（Ｐ＜０.０５）。结论：Ａｎｇ-２、ＶＥＧＦ在胃癌组织中高表达,两者在胃癌的肿瘤血管生成和进展中起重要作用。     

Does the degree of intratumoural microvessel density and VEGF expression have prognostic significance in osteosarcoma?

The role of angiogenesis as a prognostic indicator in cancer has been extensively studied in recent times with several studies demonstrating a positive correlation for various malignant tumours. However, the role of angiogenesis in osteosarcoma remains a topic of debate. In this study, we aim to evaluate the significance of intratumoural microvessel density (MVD) and the degree of vascular epithelial growth factor (VEGF) expression as markers of angiogenesis and correlate this with disease outcome. Archival paraffin-embedded pre-treatment biopsy tissue of patients treated at St. Vincent's Hospital, Melbourne, with non-metastatic osteosarcoma at initial diagnosis was reviewed. Tissue was processed for immunofluorescent staining of the microvascular endothelial cells with antibodies directed against CD31 and CD34. The degree of angiogenesis was assessed, as determined by the microvessel density (MVD). Further histological examination was performed to assess the degree of VEGF expression. Histological observations were correlated with various clinicopathological factors and patient outcome in terms of recurrence, metastasis and death. Twenty-five cases were reviewed, 15 were male and 10 were female, and the median age was 26 years (range, 13-85). The mean follow-up was 21.5 months (range, 3-75 months). The median MVD was 43 microvessels/0.26 mm2 (range, 25-54) and 46 microvessels/0.26 mm2 (range, 30-58) for CD31 and CD34, respectively. Despite the moderate to high vascularity, there was no significant difference noted between the MVD and disease outcome factors for both CD31 and CD34. There was a trend towards a higher MVD in patients aged > 40 years compared to those < 40 years (p = 0.110 for CD31 and p = 0.097 for CD34). In terms of VEGF expression, 24 of 25 cases demonstrated either moderate or strong expression; however, no prognostic significance was determined. In this study, we were able to demonstrate that osteosarcoma is a relatively vascular tumour; however, the degree of MVD and VEGF expression does not provide prognostic information. It is likely that angiogenesis plays a key role in the pathogenesis of osteosarcoma and is, therefore, a potential target for novel anti-angiogenic therapies.     

TSP-1及TP的表达与骨肉瘤新生血管生成的相关性

目的研究血小板反应蛋白-1(TSP-1)和胸苷磷酸化酶(TP)在骨肉瘤组织中的表达情况,探讨两者的平衡状态在新生血管生成中的作用。方法收集54例骨肉瘤手术切除标本,应用免疫组织化学法检测骨肉瘤组织中TSP-1及TP的表达,CD34单克隆抗体标记血管内皮细胞,计数骨肉瘤微血管密度(microvessel density,MVD)。结果骨肉瘤TSP-1的表达程度与MVD呈负相关(Spearman秩和检验:rs=-0.241,P=0.000);TP的表达与MVD计数呈正相关(Spearman秩和检验:rs=0.511,P=0.000);TSP-1、TP的表达与骨肉瘤临床病理因素无统计学意义(均P0.05),但都与肺转移显著相关(P0.05)。结论 TSP-1及TP在骨肉瘤发生发展中起重要作用,并影响血管形成及肿瘤侵袭性,两者表达的不平衡是骨肉瘤组织中新生血管生成的关键因素之一。