VEGF在非小细胞肺癌中表达与血管生成关系及临床意义

目的　采用免疫组化方法观察血管内皮生长因子 (VEGF)及血管内皮细胞膜抗原CD34在非小细胞肺癌(NSCLC)组织、肺炎性假瘤及正常肺组织中的表达状况。方法　用抗VEGF多克隆抗体及CD34单克隆抗体作免疫组化染色 ,免疫标记物阳性细胞和癌组织中微血管密度 (MVD)计数。结果　 81例NSCLC组织上VEGF表达的总阳性率为 72 .84 % ,VEGF在肺癌细胞中主要分布于胞浆、胞膜 ,少量胞外基质也有阳性表达。鳞形细胞癌阳性细胞呈弥散或局灶分布 ,腺癌则呈腺泡状分布。VEGF表达强度同非小细胞肺癌的MVD值紧密相关 ,随VEGF表达强度增高 ,MVD值亦显著增高 (P <0 .0 0 1)。结论VEGF的表达和MVD与NSCLC的发生、发展、转移关系密切 ,可作为NSCLC预后标志     

骨肉瘤中HIF-1α、VEGF、P53表达与血管生成和预后的关系

目的检测缺氧诱导因子-1α(HIF-1α)及VEGF、p53、CD34在骨肉瘤的表达，探讨其与缺氧情况下骨肉瘤血管生成和预后的关系。方法采用免疫组织化学S-P法检测46例有完整随访资料的骨肉瘤病例中HIF-1α、VEGF、p53、CD34的表达。用Spearman分析各指标间的相关性．并结合临床资料进行生存曲线分析。结果46例骨肉瘤标本中有14例(30．4％)表达HIF-1α；HIF-1α表达组VEGF、p53表达强度及术后转移率均高于HIF-1α不表达组；HIF-1α表达组患者术后1年生存率及总生存率均显著低于HIF-1α不表达组。HIF-1α表达与VEGF、p53表达之间存在显著相关性；HIF-1α表达与微血管密度(MVD)之间无相关性。结论骨肉瘤组织中存在HIF-1α的过表达，HIF-1部分地参与了骨肉瘤的演进，HIF-1通过调节VEGF的表达在骨肉瘤血管生成中发挥着重要作用；HIF-1和p53缺失或突变可能协同参与了缺氧对骨肉瘤肿瘤细胞的调节，HIF-1α表达与骨肉瘤的不良预后密切相关，是评估骨肉瘤患者预后的重要指标。     

人脑星形细胞肿瘤IL-8的表达及其与血管生成的关系

目的：探讨IL-8,VEGF在脑胶质瘤中的表达及与血管生成的关系。方法：应用由45例人脑星形细胞肿瘤和6例正常脑组织组成的组织芯片，采用免疫组织化学技术分别进行IL-8，VEGF，CD34标记并进行半定量，观测在不同病理分级胶质瘤中的表达及与微血管密度（MVD）之间的关系。结果：6例正常脑组织中不表达IL-8，VEGF。45例脑胶质瘤中，27例IL-8呈阳性表达，32例VEGF呈阳性表达，Ⅲ，Ⅳ级脑胶质瘤中IL-8，VEGF的表达比Ⅰ级、Ⅱ级明显增强，IL-8，VEGF评分为强阳性的胶质瘤内MVD明显高于评分为阴性和阳性的MVD（P<0.01）。IL-8表达与MVD呈正相关（rs=0.64，P<0.01）。VEGF表达与MVD之间呈正相关（rs=0.44，P<0.01）。IL-8表达与VEGF表达之间亦呈正相关（rs=0.56，P<0.01）。结论：IL-8，VEGF的表达与胶质瘤病理分级、MVD密切相关，二者在胶质瘤的血管生成中可能相互关联、共同调节肿瘤血管生成。     

癌组织中血管内皮生长因子表达及与微血管生成关系

目的　探讨血管内皮生长因子 (VEGF)在癌组织中的表达及其与癌组织血管生成、病理参数的关系。方法　采用S P免疫组织化学染色法检测 5 6例乳腺癌、5 9例食管癌及其癌旁正常组织各 10例的VEGF表达 ,并记数微血管密度。对每种癌组织各 10例进行VEGFmRNA原位杂交检测。结果　癌组织VEGF表达阳性率高于其正常组织 ,差异具有显著性 (P <0 0 5或P <0 0 1)。VEGF的表达与乳腺癌、食管癌的病理分级密切相关 (P <0 0 5 )。有淋巴结转移的病例 ,其VEGF表达率明显高于无淋巴结转移的病例 (P <0 0 5 )。而且随着VEGF表达的增强 ,癌组织内微血管密度明显增高 (P <0 0 1或P <0 0 5 )。结论　癌组织VEGF表达增强在肿瘤血管生成及生长、转移中起重要作用。     

胶质瘤中hTFERT、VEGF表达及其与肿瘤血管形成的关系

目的 探讨胶质瘤中端粒酶逆转录酶(hTERT)、血管内皮生长因子(VEGF)的表达与肿瘤血管形成问的相互关系.方法 分别用原位杂交和免疫组化染色检测106例胶质瘤hTERT和VEGF的表达;用CD34标记瘤组织血管内皮细胞,测定微血管密度(MVD).结果 hTERT、VEGF总阳性表达率分别为53.8%(57/106)、68.0%(72/106);hTERT或VEGF阳性分别定位于肿瘤细胞核内和细胞质内.hTERT阳性或VEGF阳性的瘤组织MVD分别为71.2±18.0和74.4±20.0;而相应的阴性组分别为60.3±21.8和58.4±23.1,两组差异均有显著性(P＜0.01).hTERT、VEGF的表达和MVD均与胶质瘤组织病理分级呈正相关(P＜0.01).结论 hTERT、VEGF的表达及MVD均与胶质瘤的恶性程度有关,前两者阳性表达,其MVD高于两者阴性表达,说明hTERT、VEGF在肿瘤血管形成中可能起促进作用.     

Smad4的表达与胰腺癌淋巴管生成之间的关系

目的观察血管内皮生长因子(VEGF)-C和Smad 4在胰腺癌组织内的表达情况,分析VEGF-C和Smad 4的表达与胰腺癌淋巴管生成及淋巴结转移之间的关系。方法取胰腺癌病例52例,其中,无淋巴结转移组12例,淋巴结转移组40例。应用免疫组化和Western blot技术检测VEGF-C和Smad4在胰腺癌组织内的表达情况。以D2-40作为淋巴管内皮标记物,观察胰腺癌组织内淋巴管生成情况。结果 VEGF-C主要表达于胰腺癌细胞胞质内,在淋巴结转移组的表达水平明显高于无淋巴结转移组。Smad4表达于胰腺癌细胞胞质和胞核内,在无淋巴结转移组的表达水平明显高于淋巴结转移组,Smad4表达阳性组淋巴管数密度明显低于Smad4表达阴性组(=0.02)。Smad4的表达与VEGF-C的表达呈显著的负相关性。结论 VEGF-C在胰腺癌淋巴管的发生及淋巴结转移中发挥重要作用,Smad4可能通过调节VEGF-C蛋白的表达抑制胰腺癌淋巴管生成和淋巴结转移。     

血管内皮生长因子和微血管密度在食管癌组织中的意义

目的 :探讨血管内皮生长因子 (VEGF)蛋白表达和微血管密度 (MVD)与食管癌临床病理的关系。方法 :应用免疫组织化学SABC法 ,以鼠抗VEGF、兔抗FⅧRAg、UEA 1抗体标记 5 2例食管癌和 5例正常食管黏膜 ,观察其在不同分化程度、浸润深度和有无淋巴结转移食管癌中的表达及MVD情况。结果 :癌组织VEGF阳性 2 8例 (5 3 9% ) ,MVD平均为 5 1 3± 14 8。VEGF蛋白表达和MVD与癌组织分化程度、淋巴结转移有关 (P <0 0 5 ,P <0 0 1) ;与癌组织浸润深度无关 (P >0 0 5 )。结论 :提示VEGF与癌组织血管发生密切相关 ,VEGF蛋白表达和MVD可作为判断食管癌的恶性程度和预后的生物学指标     

人肝癌组织中CD34和血管内皮生长因子的表达及微血管密度的 …

目的 探讨ＣＤ３４和血管内皮生长因子（ＶＥＧＦ）在人肝癌组织中的表达及微血管密度（ＭＶＤ）的病理意义。方法 对３０例人肝细胞肝癌９ＨＣＣ）及相应癌旁组织,１０例肝硬化,５例轻度慢性肝炎和４例正常肝组织,进行了ＣＤ３４、ＶＥＧＦ免疫组织化学ＳＰ法检测,对ＣＤ３４阳性血管进行ＭＶＤ计数,对ＶＥＧＦ进行半定量计数,并结合肝癌的病理特征进行分析。结果 ＨＣＣ组织中ＣＤ３４呈广泛,窦隙状阳性表达,而在正常及     

VEGF表达和MVD在乳腺癌预后中的作用

在女性乳腺癌中血管内皮生长因子 (VEGF)表达水平显著增高 ,间质微血管密度 (MVD)明显增加 ,高水平的VEGF与MVD与乳腺癌预后密切相关 ,二者联合是作为判断乳腺癌预后的重要指标。     

胸苷磷酸化酶在结直肠癌中的表达及与血管生成的关系

目的：研究结直肠癌组织中胸苷磷酸化酶（thymidine phosphorylase,TP)表达与癌组织分化程度，淋巴结转移及肿瘤内微血管密度（MVD）的关系。方法：对50例结直肠癌标本及21例正常结直肠黏膜组织进行免疫组化S－P法测定癌组织中TP的表达情况；通过CD34免疫组化染色检测癌组织中的MVD。结果：结直肠癌细胞的TP表达阳性率高于正常结直肠黏膜上皮（P＜0．01）；TP阳性组中局部淋巴结转移率高TP阴性组；TP阳性组的MVD高于TP阴性组；它们的差别均具有统计学意义，结直肠癌中高、中、低分化癌组之间的TP阳性率无明显差异。结论：癌细胞中TP的表达与肿瘤的血管生成及淋巴结转移有关。但与结直肠癌的组织化学级别无关。     

Stage I colorectal carcinoma: VEGF immunohistochemical expression, microvessel density, and their correlation with clinical outcome

Tumor–node–metastasis (TNM) stage I colorectal cancer is commonly characterized by a good prognosis, with 5-year survival around 80–90%; nonetheless, it undergoes disease progression in a percentage of cases, although the causes of adverse clinical course still remain to be elucidated. In the present study, we analyzed and compared the immunohistochemical expression of the pro-angiogenic vascular endothelial growth factor (VEGF) as well as the microvessel density (MVD) in a series of 27 surgically resected colorectal carcinomas obtained from patients deceased because of disease progression and in a cohort of 25 colorectal cancers from patients still alive with no evidence of disease progression 5 years after the initial diagnosis. The prognostic value of VEGF expression and of MVD on the overall survival to colorectal cancer was investigated. A variable VEGF immunoexpression was demonstrated in all the analyzed cases. High VEGF expression was significantly more frequent among patients deceased of the disease. These patients also displayed significantly higher MVD counts in their cancer in comparison to the patients alive after 5 years from surgery. Moreover, both high VEGF expression and MVD appeared as significant negative prognostic markers related to a shorter overall survival to stage I colorectal carcinoma, with VEGF representing an independent variable at multivariate analysis. VEGF assessment might be used in order to select those patients with a higher progression risk and to submit them to adjuvant therapies useful to prevent adverse outcome.     

COX-2 expression in ampullary carcinoma: correlation with angiogenesis process and clinicopathological variables

BACKGROUND: There is evidence that the anti-neoplastic effect of non-steroidal anti-inflammatory drugs is attributable to cyclooxygenase-2 (COX-2) inhibition, but the exact mechanisms whereby COX-2 can promote tumour cell growth remain unclear. One hypothesis is the stimulation of tumour angiogenesis by the products of COX-2 activity. To data, there have been few clinicopathological studies on COX-2 expression in human ampullary carcinoma and no data have been reported about its relation with tumour angiogenesis. Objective: To investigate by immunohistochemistry the expression of COX-2 and the angiogenesis process in a series of primary untreated ampullary carcinomas. METHODS: Tissue samples from 40 archival ampullary carcinomas were analysed for COX-2, vascular endothelial growth factor (VEGF), and an endothelial cell marker von Willebrand factor (vWF) by immunohistochemistry, using specific antibodies. RESULTS: COX-2 expression was detected in 39 tissue samples (97.5%), of which two (5%) were graded as weak, 26 (65%) as moderate, and 11 (27.5%) as strong. Only one lesion (2.5%) was negative for COX-2 expression. VEGF expression was detected in 36 tissue samples (90%). A significant positive correlation was found between COX-2 and VEGF expression. No statistic correlation was found between COX-2 expression and microvessel density. CONCLUSIONS: COX-2 is highly expressed in ampullary carcinomas. This suggests an involvement of the COX-2 pathway in ampullary tumour associated angiogenesis, providing a rationale for targeting COX-2 in the treatment of ampullary cancer.     

Evaluation of PRL-3 expression, and its correlation with angiogenesis and invasion in hepatocellular carcinoma

Protein phosphatase of regenerating liver 3 (PRL-3) is a metastasis-associated phosphatase. Studies have shown that its overexpression increases cell motility and invasiveness. In this study, we aimed to investigate the expression of PRL-3 in hepatocellular carcinoma (HCC) tumor tissues and determine its correlations with matrix metalloproteinases (MMP-2, MMP-9) and E-cadherin in HCC. Paired cancerous and non-cancerous tissues were freshly collected from 42 primary HCC patients. PRL-3 expression at both mRNA and protein level was evaluated by real-time PCR, Western blot analysis and immunohistochemistry. The microvessel density (MVD) in HCC was detected with immunohistochemistry. The mRNA expression of MMP-2, MMP-9 and E-cadherin was analyzed by real-time PCR in search of correlations with PRL-3. We found that PRL-3 was significantly up-regulated in the HCC tumor tissues compared with corresponding noncancerous liver tissues (0.664+/-0.053 vs. 0.024+/-0.003, P<0.001). The mRNA level of PRL-3 in tissues was correlated with serum alpha-fetoprotein level, vascular invasion and metastasis (P<0.001). PRL-3 expression was closely related to MVD. Furthermore, we found a significant correlation between PRL-3 mRNA expression and MMP-2, MMP-9 and E-cadherin. Our results demonstrated that PRL-3 is up-regulated in HCC. It is strongly suggested that PRL-3 plays a key role in the angiogenesis and invasion of HCC. MMP-2, MMP-9 and E-cadherin might be involved in PRL-3 functions in HCC.     

Correlation between PSMA and VEGF expression as markers for LNCaP tumor angiogenesis

Our aim is the identification and correlation of changes in tumor-associated protein expression which results from therapy. LNCaP tumors, excised from nude mice treated either by orchiectomy or with the chemotherapeutic agent paclitaxel, were evaluated for the expression of proteins and receptors associated with growth, differentiation, and angiogenesis using immunohistologic procedures. Compared to untreated control tumors, both treatments reduced the expression of vascular endothelial growth factor (VEGF), prostate-specific membrane antigen (PSMA), prostate-specific antigen (PSA), androgen receptor (AR), and epidermal growth factor receptor (EGFR). The effect of paclitaxel treatment on AR expression was the most significant (P = .005). Of particular interest was identifying a significant correlation (P < .000801) between PSMA and VEGF expression regardless of treatment modality. These altered expressions suggest that PSMA may also be a marker for angiogenesis and could represent a target for deliverable agents recognizing either prostatic tumors or endothelial development. Cell surface PSMA would then present a unique target for treatment of patients early in their development of prostatic metastases.     

VEGF expression and angiogenesis in oral squamous cell carcinoma: an immunohistochemical and morphometric study

Angiogenesis is involved in tumor progression of oral squamous cell carcinoma (OSCC). In this study, we have investigated by immunohistochemistry vascular endothelial growth factor (VEGF) expression in tumor cells and we have correlated VEGF expression to microvessel area, evaluated by using CD105 as a marker of endothelial cells, in bioptic specimens of 54 human OSCC. Results demonstrated that VEGF is highly expressed in OSCC tumor specimens when compared to pre-neoplastic and normal tissues, without differences between the edge and inside the tumor. Moreover, VEGF expression is reduced in poor differentiated OSCC tumors when compared to moderate and good differentiated forms, and tumor microvessel area is higher in tumors when compared to pre-neoplastic lesions and normal tissues. Finally, VEGF and CD105 may be considered as reliable markers of tumor angiogenesis and progression in OSCC, even if we did not demonstrate any correlation between VEGF expression, tumor microvascular area, clinical stage, and lymph node status.     

存活素和尿激酶型纤溶酶原激活剂在人胰腺癌组织中的表达意义及相关性分析

目的分析存活素(Survivin)和尿激酶型纤溶酶原激活剂(u PA)在人胰腺癌中的表达及两者之间的相关性。方法采用免疫组化PV法检测原发性胰腺癌组织(63例)及癌旁非肿瘤胰腺组织(11例)中Survivin和u PA的表达,分析两者间表达的相关性及与胰腺癌临床病理特征的关系。结果 63例胰腺癌组织中Survivin和u PA阳性率分别为69.8%(44/63)、65.1%(41/63),11例癌旁非肿瘤胰腺组织中均无表达,Survivin和u PA表达呈正相关(r=0.389,P0.050),两者与胰腺癌TNM分期、分化程度及淋巴结转移均有关(P均0.05)。结论 Survivin和u PA在胰腺癌组织中的表达呈正相关,两者表达上调在胰腺癌的发生、发展、侵袭和转移中起重要作用。     

Pleiotropic effects of CXC chemokines in gastric carcinoma: differences in CXCL8 and CXCL1 expression between diffuse and intestinal types of gastric carcinoma

CXC chemokines modulate host immunity, neovascularization, growth and invasive behaviour of tumours. Despite their relevance in tumour biology, chemokine expression in intestinal- and diffuse-type gastric carcinoma, which exhibit a completely different growth pattern, has not been investigated in detail. In this study, expression of the CXC chemokines CXCL8 [interleukin (IL)-8], CXCL1 [growth-related oncogene alpha (Gro alpha)], CXCL9 [monokine induced by interferon (IFN)-gamma] and CXCL10 [IFN-gamma-inducible protein-10 (IP-10)] and the corresponding chemokine receptors CXCR1-3 was investigated by immunohistochemistry in intestinal- and diffuse-type gastric carcinoma. Tumour cells of all patients expressed CXCL8. CXCL8 expression was significantly stronger in tumour cells of diffuse- rather than intestinal-type gastric carcinoma (P < 0.01) as determined by a semiquantitative score. CXCL1 was expressed almost exclusively by diffuse- but not intestinal-type carcinoma cells. The corresponding chemokine receptors, CXCR1 and CXCR2, were found on carcinoma cells. Furthermore, CXCL8 expression correlated with number of tumour vessels (P < 0.01), suggesting an angiogenetic function in gastric carcinoma not only in vitro but also in vivo. CXCL10 and CXCL9, attractants for T cells, were expressed by peritumorous macrophages in close proximity to IFN-gamma-producing CXCR3-positive T cells in both tumour types. These chemokines may attract gastric carcinoma-infiltrating T cells via an IFN-gamma-mediated pathway and enhance host immunity against the tumour. In gastric carcinoma a complex interplay between CXC-chemokine signals derived from both tumour cells and tumour-infiltrating immune cells may exhibit pleiotropic effects in tumour biology that go far beyond their originally described functions as leucocyte chemoattractants. Because CXCL8 and CXCL1, which are known to increase growth and invasive behaviour of malignant tumours, are significantly stronger expressed in diffuse- than intestinal-type gastric carcinoma, one may speculate that these chemokines influence the different growth pattern of gastric carcinoma types.     

CSF-1R和VEGF在人声门上型喉癌的表达及与淋巴结转移的关系

目的研究巨噬细胞集落刺激因子受体(macrophage colony-stimulating factor receptor,CSF-1R)和血管内皮生长因子(vascular endothelial factor,VEGF)在声门上型喉鳞状细胞癌的表达及其与喉癌淋巴结转移之间的关系。方法应用免疫组化方法对30例无淋巴结转移的声门上型喉癌组织标本,15例有淋巴结转移的声门上型喉癌组织标本及10例正常喉组织粘膜标本中CSF-1R和VEGF的蛋白表达进行检测,并对其与喉癌相关的临床病理参数进行统计学分析。结果 CSF-1R和VEGF在声门上型喉鳞癌组织中呈强阳性表达,表达水平显著高于对照组(P<0.05),其中有淋巴结转移组明显高于无淋巴结转移组(P<0.05)。结论 CSF-1R和VEGF在声门上型喉癌过表达与淋巴结转移呈正相关。