血管内皮生长因子、微血管密度在子宫平滑肌瘤中的表达及其意义

目的:探讨米非司酮对子宫平滑肌瘤患者血管内皮生长因子(VEGF)的表达及微血管生成的影响。方法:采用免疫组化S-P法检测60例子宫平滑肌瘤VEGF的表达及计数微血管密度(MVD),其中40例为米非司酮服用者,20例未服用者为对照。结果:米非司酮组子宫平滑肌瘤VEGF表达阳性率为37.5%,MVD为9.90±5.95;未服用组平滑肌瘤VEGF的阳性率为80.0%,MVD为16.36±2.07;两组间差异有统计学意义(P<0.05)。38例用药后肌瘤中缩小明显者(直径缩小≥2cm)VEGF表达阳性率为12.0%,MVD为7.89±4.36,亦低于缩小不明显者(直径缩小<2cm)VEGF阳性表达率(80.0%)和MVD(11.29±3.10)表达,差异有统计学意义(P<0.05)。结论:口服米非司酮患者中,子宫肌瘤VEGF和MVD呈低表达,提示其可抑制肿瘤血管生成并抑制肌瘤生长。     

血管内皮生长因子及微血管密度在乳腺癌中的表达及意义

目的 研究血管内皮生长因子(VEGF)及微血管密度(MVD)在乳腺癌组织中的表达及意义。方法 应用免疫组化SP法检测81例原发性乳腺癌患者癌组织MVD和VEGF的表达。结果 VEGF高表达者49例(60．5％)，MVD计数高者35例(43．2％)。VEGF、MVD与肿瘤TNM分期有关，但与年龄、肿瘤大小、雌激素受体(ER)表达及淋巴结状况无关；VEGF与MVD的表达有显著相关性。单因素预后分析显示，MVD及VEGF低表达者无病生存期(DFS)及总生存期(OS)长于高表达者。分组的单因素分析表明，VEGF与各组患者的DFS有显著相关性，与淋巴结( )和Ⅲ期乳腺癌患者的OS有显著相关性；而MVD与淋巴结( )患者的DFS和OS以及Ⅲ期乳癌患者的DFS有显著相关性。多元回归分析显示，MVD是风险因子，表达越高生存期越短。结论 VEGF和MVD均为判断乳腺癌须后的有效指标，其中MVD可能是预测乳腺癌预后的独立因子。     

胃癌组织中环氧化酶-2的表达与微血管密度和VEGF的关系

目的 :探讨环氧化酶 -2 (COX 2 )在胃癌组织中的表达及其与微血管密度(microvesseldensity ,MVD)和血管内皮生长因子 (vascularendothelial growthfactor ,VEGF)的关系。方法 :采用免疫组织化学法 ,检测 43例胃癌患者手术切除标本中COX 2和VEGF的表达 ,并计数MVD。结果 :COX 2在胃癌组织的阳性表达率为60 5 % ,明显高于对照组 ,P <0 0 1;并且与胃癌淋巴结的转移和临床分期有关 ,与肿瘤大小、浸润深度、分化程度均无关。COX 2和VEGF表达一致符合率为 5 3 5 % ,两者表达有显著相关性 ,P <0 0 1。COX 2阳性和VEGF阳性组MVD值 (2 2 0 8± 3 69、2 2 12± 3 5 0 )均高于COX 2阴性和VEGF阴性组 (17 68± 3 5 0、16 15± 3 2 3 ) ,P <0 0 5 ;COX 2和VEGF均为阳性者的MVD值最高 (2 2 86± 3 40 ) ,P <0 .0 5。结论 :COX 2、VEGF的表达以及MVD的测定可作为判断胃癌恶性潜能的重要生物指标。COX 2、VEGF的表达对肿瘤血管形成可能起重要作用 ,联合检测COX 2、VEGF的表达对了解肿瘤血管形成的机制有一定的作用     

血管内皮生长因子在人脑胶质瘤中的表达及意义

目的研究人脑胶质瘤中血管内皮生长因子(vascularendothelialgrowthfactor,VEGF)的表达及临床病理意义.方法应用SABC免疫组化技术检测67例人脑胶质瘤、8例正常脑组织中VEGF表达.结果VEGF仅在肿瘤组织中表达,阳性表达率为83.6%,而在正常脑组织中无表达.VEGF与胶质瘤恶性程度(P<0.01)及肿瘤复发(P<0.01)相关.结论胶质瘤细胞能分泌VEGF,VEGF表达与肿瘤复发及预后有关.     

Expression of Vascular Endothelial Growth Factor-C and Vascular Endothelial Growth Factor Receptor-3 in Ovarian Epithelial Tumors

Objective： To explore the role of vascular endothelial growth factor-C （VEGF-C） in the process of angiogenesis, lymphangiogenesis and lymphatic metastasis in epithelial ovarian tumors. Methods： In situ hybridization and immunohistochemical staining for VEGF-C were performed in 30 epithelial ovarian carcinomas, 9 borderline tumors and 26 benign tumors. Endothelial cells were immunostained with anti-VEGFR-3 pAb and anti-CD31 mAb, and VEGFR-3 positive vessels and microvessel density （MVD） were assessed by image analysis. Results： VEGF-C mRNA and protein expression were detected in cytoplasm of carcinoma cells. VEGF-C mRNA and protein expression in ovarian epithelial carcinomas were significantly higher than those in borderline tumors and benign tumors （P〈0.05 or P〈0.01）. In ovarian epithelial carcinomas, VEGF-C protein expression, VEGFR-3 positive vessels and MVD were significantly higher in the cases of clinical stage Ⅲ-Ⅳ and with lymph node metastasis than those of clinical stage Ⅰ-Ⅱ and without lymph node metastasis respectively （P〈0.05 or P〈0.01）. VEGFR-3 positive vessels and MVD were significantly higher in VEGF-C protein positive tumors than negative tumors （P〈0.05）. VEGFR-3 positive vessels was significantly correlated with MVD（P〈0.01）. Conclusion： VEGF-C might play a role in lymphatic metastasis via lymphangiogenesis and angiogenesis in epithelial ovarian tumors, and VBEGF-C could be used as a biologic marker of metastasis in ovarian epithelial tumors.     

Lymphatic vessel density and vascular endothelial growth factor-C expression correlate with malignant behavior in human pancreatic endocrine tumors.

Metastatic dissemination of tumor cells to regional lymph nodes is a common early feature of many human cancers including pancreatic adenocarcinoma. In contrast, lymph node metastasis is more variably observed in pancreatic endocrine tumors. The objective of this study was to assess the lymphatic system of human pancreatic endocrine tumors and correlate this to clinical behavior. Immunohistochemistry was performed using antibodies to two recently identified markers of lymphatic endothelium, namely, LYVE-1 and podoplanin, and to the lymphangiogenic factor vascular endothelial growth factor (VEGF)-C. As has been reported previously, we observed that in the normal pancreas, islets of Langerhans are devoid of intra-islet lymphatics, but that lymphatics are present in connective tissue in association with ducts and blood vessels. We found that both benign and malignant pancreatic endocrine tumors contain intratumoral lymphatic vessels. Lymphatic vessel density was related to the size of the tumor in benign tumors and to the presence of liver metastasis but not to lymph node metastasis in malignant tumors. VEGF-C was expressed in tumor cells: 4 of 19 (21%) benign tumors were positive, whereas 6 of 9 (67%) borderline tumors and 9 of 11 (82%) carcinomas were positive. These findings strongly suggest that lymphangiogenesis occurs in pancreatic endocrine tumors and that lymphatic invasion and the development of metastases are associated with VEGF-C expression.     

Prognostic significance of vascular endothelial growth factor expression in human ovarian carcinoma

The influence of vascular endothelial growth factor (VEGF) expression and microvessel density (MVD) on prognosis and the relationship between VEGF expression and MVD in ovarian carcinoma are not well defined. We studied VEGF expression in parallel with MVD by immunohistochemistry in 94 ovarian tumours (64 malignant, 13 borderline, and 17 benign) and correlated the results with the clinicopathologic prognostic factors of the disease to clarify their significance in this disease. Assessment of VEGF mRNA isoforms by RT-PCR was also performed. Of the malignant, borderline, and benign ovarian tumours respectively, two (3%), four (31%) and 16 (94%) were negative, 31 (48%), seven (54%) and one (6%) had low expressions, and 31 (48%), two (15%) and none (0%) had high expressions of VEGF. There were significant associations between the VEGF expression and disease stage (P= 0.002), histologic grade (P= 0.0004), and patient outcome (P= 0.0002). MVD did not correlate significantly with the clinicopathologic parameters. Likewise, no correlation was found between MVD and VEGF expression. The survival of patients with high VEGF expression was significantly worse than that of patients with low and negative VEGF expression (P = 0.0004). Multivariate analysis revealed that disease stage and VEGF expression were significant and independent prognostic indicators of overall survival time (P = 0.008 and P = 0.006 respectively). These findings suggest that in conjunction with the established clinicopathologic prognostic parameters of ovarian carcinoma, VEGF expression may enhance the predictability of patients at high risk for tumour progression who are potential candidates for further aggressive therapy.     

介入化疗对直肠癌血管内皮生长因子及微血管的影响

目的　探讨介入化疗对直肠癌血管内皮生长因子表达 (VEGF)及微血管计数 (MVD)的影响。方法　对 3 4例直肠癌患者介入化疗前后的肿瘤组织 ,用CD3 4对VEGF表达进行测定 ,并进行MVD计数。结果　本组患者介入化疗前及后 4至 5周VEGF阳性表达率分别为 61.7% (2 1/3 4)、3 2 .4% (11/3 4) ,MVD计数明显降低 ,差异均有显著性意义(P <0 .0 1)。结论　介入化疗能降低直肠癌组织VEGF的表达 ,减少MVD计数 ,提示介入化疗可能调节直肠癌的分化程度 ,减少术后转移。     

血管内皮生长因子表达及微血管密度与放射敏感性

血管内皮生长因子(VEGF)是一种具有肝素结合活性的生长因子,能特异作用于血管内皮细胞,对血管生长有极强R诱导作用.VEGF的表达与肿瘤内微血管密度(MVD)呈明显正相关.缺氧是VEGF表达最主要的调节因素.恶性肿瘤在生长过程中,由于组织增生过快必然会造成局部组织缺氧,从而诱导VEGF表达;而乏氧细胞对射线抗拒.所以,有希望以VEGF的表达及MVD来预测放射敏感性.     

Survivin、VEGF的表达及微血管密度与非小细胞肺癌临床病理特征的关系

背景与目的研究发现,Survivin在大多数肿瘤中有表达,但在成人组织不表达或低表达,且参与肿瘤血管形成。本研究中我们主要检测非小细胞肺癌(non鄄smallcelllungcancer,NSCLC)、癌旁及肺良性病变组织中凋亡抑制基因Survivin及血管内皮生长因子(vascularendothelialgrowthfactor,VEGF)的表达和微血管密度(microvesseldensity,MVD)值,并探讨三者间的相互关系。方法应用免疫组化(S鄄P)法检测96例NSCLC组织中Survivin、VEGF及MVD。分析Survivin、VEGF及MVD与NSCLC临床病理特征的关系,以及Survivin、VEGF、MVD间的相互关系。结果NSCLC组织中Survivin阳性率69.8%(67/96),明显高于癌旁(16.1%)和肺良性病变组织(0%)(P<0.01),其表达与肿瘤分化程度、TNM分期有关。VEGF在肺癌、癌旁、肺良性病变组织中的阳性率分别为72.9%(70/96)、45.2%(14/31)和25.0%(5/20)(P<0.05),其表达与肿瘤的TNM分期及淋巴结转移有关。肺癌、癌旁、肺良性病变组织中MVD值分别为24.44±7.79、19.37±5.26、11.83±6.25,且MVD值的高低与肿瘤大小、淋巴结转移和TNM分期有关(P<0.05)。Survivin在肺癌组织中的表达与VEGF、MVD密切相关,随着Survivin强度的增加VEGF分级及MVD值亦增加。结论不同性质的肺病变组织中Survivin、VEGF的表达水平和MVD值不同,NSCLC中Survivin表达明显增高,其表达与肿瘤分化、分期有关;Survivin的过度表达与NSCLC的血管生成有关,细胞凋亡与血管生成在肺癌的发生发展中起协调作用。     

Expression and localization of vascular endothelial growth factor receptors in human hepatocellular carcinoma and non-HCC tissues

Flt-1 (VEGF receptor-1) and KDR/Flk-1 (VEGF receptor-2) are the high-affinity receptors for the angiogenesis factor, vascular endothelial growth factor (VEGF). VEGF expression has been confirmed in human hepatocellular carcinoma (HCC), and VEGF is thought to be involved in the angiogenesis within HCC tissues. However, expressions of VEGF receptors in HCC have not been reported. We immunohistochemically examined expressions and localizations of Flt-1 and KDR in 28 surgically resected HCC tissues. In non-cancerous area, Flt-1 and KDR were mainly found in macrophages including Kupffer cells; both receptors were found in vascular endothelial cells in the portal veins and arteries within portal tracts; and KDR was also found in some sinusoidal endothelial cells. In cancerous area, Flt-1 and KDR were found in some macrophages, and also in the endothelial cells of intratumoral blood vessels. In 25 moderately and/or poorly differentiated HCCs, KDR expression in the blood space endothelial cells was clear and continuous in 20 cases, and focal in 5 cases. These results suggest that there would be an angiogenesis mechanism via VEGF/Flt-1 or VEGF/KDR in HCC, and the VEGF/KDR system would take a more important role.     

Correlational study of vascular endothelial growth factor expression and microvessel density in primary malignant gastric lymphoma

Vascular endothelial growth factor (VEGF) expression and microvessel density (MVD) in primary malignant gastric lymphoma were studied, and their correlation as well as its clinical significance was analyzed. Thirty-five patients diagnosed with primary malignant gastric lymphoma were enrolled in this study. VEGF expression in the tumor tissues was detected by immunohistochemistry. Microvessel density in tumors was counted with Weidner's method and compared with MVD in normal tissues 5 cm away from tumor site. Collected data were analyzed statistically. Our results showed that VEGF expression and MVD in tumor tissues were higher than those in normal tissues, and the difference between these two groups was significant (P < 0.01). As VEGF expression was elevated, MVD was also increased in tumor tissues. Statistical analysis revealed that VEGF expression was positively correlated with MVD (r = 0.392, P < 0.05). VEGF was highly expressed in primary malignant gastric lymphoma and positively correlated with MVD. These results strongly suggest that anti-angiogenesis therapy investigated in gastric lymphoma is a prospective clinical trial.     

Frequent expression of the vascular endothelial growth factor in human non-small-cell lung cancers

BACKGROUND: Angiogenesis is an essential factor for progression and metastases in solid tumors. It has been reported that several angiogenic factors play a role in the regulation of angiogenesis. Vascular endothelial growth factor (VEGF) is one of the most important molecules in angiogenesis. We investigated expressions of VEGF in a series of lung carcinomas with regard to clinicopathological factors. METHOD: VEGF expression was investigated by use of immunohistochemical studies and Northern blot analysis, using 155 primary and 26 metastatic lung carcinomas for the immunohistochemical studies and 10 primary and two metastatic lung carcinomas for the Northern blot analysis. All lesions were resected at surgery. RESULTS: The frequencies for positive VEGF expression were 64 of 74 (86.5%) adenocarcinomas, 38 of 67 (56.7%) squamous cell carcinomas, four of four (100%) large cell carcinomas, two of three (66.7%) adenosquamous carcinomas and one of five (20%) small-cell carcinomas, the degree of positivity generally being greater in well differentiated tumors. The majority of metastatic foci from adenocarcinomas and squamous cell carcinomas at other sites were also positive (76.5 and 66.7%, respectively). VEGF expression did not correlate with clinicopathological factors such as tumor size or pathological stage, but pathological stage I adenocarcinoma cases positive for VEGF demonstrated a shorter disease-free period when followed up for 48 months than those cases expressing VEGF negatively. CONCLUSIONS: The results indicated that VEGF expression was frequently detected in non-small-cell lung cancers and suggested that VEGF might relate to the disease-free period of the patients with early adenocarcinomas.      

Combined analysis of vascular endothelial growth factor and platelet-derived endothelial cell growth factor expression in gastric carcinoma

Solid tumours require neovascularization for growth and metastasis. Both vascular endothelial growth factor (VEGF) and platelet-derived endothelial cell growth factor (PD-ECGF) are well-characterized inducers of angiogenesis. In this study we examined the expressions of these antigens and their relationship with microvessel density and also determined their prognostic significance. Ninety-five specimens resected from patients with gastric carcinoma were investigated using immunohistochemical methods. Microvessel density, determined by immunostaining for factor VIII-related antigen, was significantly higher in tumours that were both VEGF⁺ and PD-ECGF⁺ than in tumours that were both VEGF⁻ and PD-ECGF⁻. According to prognosis, patients with VEGF⁺ tumours had a significantly worse prognosis than did those with VEGF⁻ tumours. Although there was no significant correlation between PD-ECGF expression and prognosis, patients with PD-ECGF⁺ tumours tended to have a shorter survival than did those with PD-ECGF⁻ tumours. Moreover, the frequency of hepatic recurrence was significantly higher in patients with tumours that were both VEGF-positive and PD-ECGF⁺ than in all other patients. Int. J. Cancer 74:545–550, 1997. © 1997 Wiley-Liss, Inc.     

血管内皮生长因子在人脑胶质瘤侵袭中的作用

 目的　研究血管内皮生长因子 (Vascularendothelialgrowthfactor ,VEGF)在脑胶质细胞瘤中的表达情况 ,探讨其表达与肿瘤的恶性程度、肿瘤侵袭及预后的关系。方法　采用免疫组织化学染色检测 5 2例脑胶质瘤标本 ,4例垂体腺瘤 ,5例正常脑组织的VEGF表达水平。结果　在正常脑组织中未见VEGF免疫组化染色阳性细胞 ,垂体腺瘤偶有表达 ,脑胶质瘤组织中均有VEGF表达 (P <0 .0 5 )。随着脑胶质瘤恶性程度的增加 ,VEGF的表达增高 (P <0 .0 1)。生存期 <3年者VEGF的表达显著高于生存期 >3年者 (P <0 .0 1)。结论　VEGF的表达与胶质瘤的恶性程度和侵袭性等有关 ,并对其预后有一定的意义     

人星形细胞瘤血管内皮生长因子表达

目的:探讨VEGF在星形细胞瘤中表达与星形细胞瘤组织学分级和患者年龄的关系.方法:应用免疫组化方法检测52例星形细胞瘤石蜡包埋病理切片.结果:VEGF在不同病理级别星形细胞瘤中表达程度不同,随组织级别增加,表达增强.VEGF高表达组患者平均年龄高于低表达组.结论:VEGF与星形细胞瘤生长及恶性进展关系密切,VEGF高表达与高龄有关,预示预后不良.     

Cyclooxygenase-2 upregulates vascular endothelial growth factor expression and angiogenesis in human gastric carcinoma

Although gastric cancer with cyclooxygenase (COX)-2 overexpression is associated with poor prognosis, the mechanistic pathway remains unknown. We examined the associations between expressions of COX-2 and vascular endothelial growth factor (VEGF) in both gastric cancer cells and in human gastric cancer. The gastric cell line, Kato III, was transiently transfected with cox-2 expressing vector. The levels of COX-2, prostaglandin (PG) E2 and VEGF expression were measured post-transfection. Additionally, expressions of COX-2 and VEGF in human gastric cancer were determined by immunohistochemistry in archive gastrectomy specimens. Tumor angiogenesis was assessed by the microvessel density (MVD), which was determined by anti-CD34 immunostaining. Transient transfection of Kato III with cox-2 was associated with increased COX-2 expression, higher PGE2 production and upregulated VEGF expressions. Treatment with NS398, a specific COX-2 inhibitor, reduced VEGF expression in COX-2 expressing Kato III cells by 25%. Among the 67 gastric cancers examined, COX-2 overexpression was found in 45 (67%) cases whereas increased VEGF expression was detected in 46 (69%) cases. There was a significant association between COX-2 and VEGF expressions in gastric cancer (r=0.25, p=0.041). Additionally, tumor MVD was associated with both COX-2 (r=0.32, p=0.008) and VEGF (r=0.39, p=0.001) expressions. Our results showed that overexpression of COX-2 in both gastric cells and primary gastric cancer is associated with upregulation of VEGF and angiogenesis. Future studies should evaluate the potential anti-angiogenic effect of COX-2 inhibitors on human gastric cancer.