乳腺癌血清VEGF水平与癌组织中VEGF和COX-2表达及微血管密度的关系

目的探讨乳腺癌患者血清血管内皮生长因子(sVEGF)水平与乳腺癌血管生成的关系。方法采用酶联免疫吸附试验(ELISA)检测68例乳腺癌、35例乳腺良性病变和20例健康女性的sVEGF水平,免疫组化S-P法检测相应乳腺癌组织中VEGF、环氧合酶-2(COX-2)及微血管密度(MVD)表达水平,并分析sVEGF水平与VEGF、COX-2及MVD表达的关系。结果(1)健康女性组、乳腺良性病变组和乳腺癌组sVEGF浓度中位数分别为105.93、150.82和306.51 pg/ml,乳腺癌组明显高于健康女性组。(2)乳腺癌组VEGF和COX-2表达阳性率分别为67.6%和44.1%,乳腺良性病变组VEGF和COX-2表达阳性率分别为42.9%和11.4%,两组间差异有统计学意义(P值分别为0.015和0.002)。(3)乳腺癌患者sVEGF水平与癌组织中VEGF、COX-2及MVD表达均呈正相关。(4)乳腺癌患者中,VEGF表达阳性组COX-2阳性率(65.21%)明显高于VEGF表达阴性组(18.18%); COX-2表达阳性组MVD(22.94±5.51)明显高于COX-2表达阴性组(10.30±4.42)。结论乳腺癌患者sVEGF水平明显增高于健康女性,并与癌组织中VEGF、COX-2及MVD表达呈正相关。     

Serum interleukin 6, plasma VEGF, serum VEGF, and VEGF platelet load in breast cancer patients

Serum and plasma concentrations of vascular endothelial growth factor (sVEGF and pVEGF), serum concentrations of interleukin 6 (IL-6), and VEGF platelet load (VEGF/pl) in the blood of healthy controls (n = 26), breast cancer patients with locoregional disease (n = 31), and patients with progressive advanced disease (n = 73) have been compared. The 95th percentile values for the control population were 250 pg/mL for sVEGF, 30 pg/mL for pVEGF, and 1.6 pg/mL for IL-6. The 95th percentile value of the calculated VEGF/pl was 1.0 pg/10(6) platelets in the control population. Serum VEGF concentrations correlated with platelet number in all the groups. Patients with thrombocytosis had a median sVEGF concentration of 833 pg/mL, compared to 249 pg/mL in other patients (P = 0.018). Serum IL-6 levels correlated with sVEGF levels and with the calculated VEGF/pl. Serum IL-6 concentration was significantly higher in patients with breast cancer compared to healthy controls (P < 0.0001). Median IL-6 serum levels were nearly 10 times higher in patients with metastatic breast cancer as compared to the those with locoregional disease (6.0 pg/mL versus 0.7 pg/mL, respectively). Plasma VEGF and the VEGF/pl were also significantly different in the 3 groups. The ratio between sVEGF and pVEGF tended to be smaller in the metastatic breast cancer group compared to the patients with locoregional disease (median, 7.5 versus 10.1, respectively; P = 0.066), suggestive of more intravasal platelet degranulation in the former group. Serum IL-6 level is the most discriminative factor separating healthy controls and the locoregional and metastatic breast cancer patient groups. These results suggest a role for tumor-derived IL-6 in regulating VEGF expression in platelets and their precursors and also confirm the role of circulating platelets in the storage of VEGF.     

VEGF在前列腺癌中的表达及与肿瘤MVD的关系

目的:研究前列腺癌组织中的血管内皮生长因子（VEGF）表达与前列腺癌肿瘤微血管密度（MVD）的关系。方法:选取81例确诊前列腺癌患者及良性前列腺增生患者52例。采用免疫组化法进行染色,观察两种组织中VEGF、MVD的表达情况,并分析VEGF与前列腺癌患者的临床病理特征关系及与MVD之间的关系。结果:前列腺癌组织中VEGF阳性表达率（69.14%）显著的高于前列腺良性增生组（28.85%）,差异具有统计学意义（P<0.05）。前列腺癌组织中MVD计数为（36.7±8.2）显著高于前列腺良性增生组（19.3±5.8）,差异具有统计学意义（P<0.05）。前列腺癌组织中VEGF表达阳性率与患者的TNM分期、淋巴结转移、分化程度具有显著关联（P<0.05）。VEGF表达阳性的癌组织中MVD（40.3±7.5）显著多于VEGF表达阴性的癌组织（28.7±6.1）,差异具有统计学意义（P<0.05）。结论:前列腺癌组织中VEGF高表达,MVD生成增多,VEGF与患者的临床病理特征具有一定的关系,VEGF阳性表达患者的MVD增生水平越高。     

血管内皮生长因子及色素上皮衍生因子在乳腺癌中的表达及临床意义

目的：探讨血管内皮生长因子（VEGF）、色素上皮衍生因子（PEDF）在乳腺癌组织中的表达水平及其与乳腺癌病理特征的关系。方法采用Envision免疫组织化学方法对20例乳腺良性病变组织（纤维腺瘤）、85例乳腺浸润性导管癌组织中的VEGF、PEDF和CD34表达情况进行检测。 CD34表达反映微血管密度（ MVD ）。计数资料采用χ2检验, Spearman 等级相关分析方法进行相关性分析。结果 VEGF 在乳腺癌组织中的阳性表达率为71.7％（61/85）,高于在乳腺良性组织中的阳性表达率40％（8/20）,差异有统计学意义（χ2＝9.959, P＝0.002）;PEDF在乳腺癌组织中的阳性表达率为41.2％（35/85）,低于在乳腺良性组织中的阳性表达率90％（18/20）,差异有统计学意义（χ2＝19.683, P＝0.000）。在乳腺癌组织中VEGF与PEDF表达呈负相关（ r＝-0.365, P＝0.019）。乳腺癌组织中VEGF表达与肿瘤直径（χ2＝26.31,P＝0.000）、TNM分期（χ2＝5.428,P＝0.020）、淋巴结转移有关（χ2＝5.368, P＝0.021）;PEDF表达与TNM分期（χ2＝8.584, P＝0.003）、肿瘤直径（χ2＝11.079,P＝0.001）、绝经状态（χ2＝4.507,P＝0.034）、ER状态有关（χ2＝3.974,P＝0.046）。 MVD值在PEDF阴性组高于阳性组（38.67±6.52比22.56±5.16,Z＝-0.984,P＝0.000）,在VEGF阳性组则高于阴性组（38.78±6.28比25.36±5.12,Z＝-0.972,P＝0.000）。结论乳腺癌组织中存在PEDF、VEGF的表达相关性,且与MVD相关,对认识乳腺癌的生物学特性以及指导乳腺癌的诊疗具有重要意义。     

血管内皮生长因子C蛋白在乳腺癌组织中的表达及其意义

目的:研究血管内皮生长因子C(VEGF-C)蛋白在乳腺癌组织中的表达及意义。方法:采用免疫组化法对60例乳腺癌、12例良性乳腺病变组织中VEGF-C的表达进行检测,探讨其与微血管密度(MVD)、微淋巴管密度(MLD)、增殖细胞核抗原(PCNA)蛋白及临床病理因素之间的相关性。结果:乳腺癌组织中VEGF-C表达水平高于良性乳腺病变组织(u=137.5,P=0.001)。乳腺癌组织中VEGF-C表达与MVD无相关性(P=0.951),而与MLD(r=0.286,P=0.027)及PCNA(r=0.315,P=0.014)有相关性;VEGF-C(r=0.389,P=0.002)、MLD(r=0.335,P=0.009)与患者淋巴结转移状况相关,与其他临床病理因素无相关性。单因素Logistic回归分析显示,高VEGF-C、MLD组发生淋巴结转移的风险分别是低VEGF-C、MLD组的4.059倍(95%CI为1.234～13.349,P=0.021)和3.519倍(95%CI为1.209～10.240,P=0.021)。多因素Logistic回归分析显示,VEGF-C对淋巴结转移的影响独立于MLD。结论:乳腺癌组织中VEGF-C蛋白表达水平升高,VEGF-C在乳腺癌淋巴管生成及淋巴结转移中起重要作用,且它对淋巴结转移的影响独立于MLD。另外,VEGF-C高表达的患者肿瘤细胞的增殖性较强。     

Association between immunohistochemical expression of vascular endothelial growth factor (VEGF), VEGF-expressing neuroendocrine-differentiated tumor cells, and outcome in prostate cancer patients subjected to watchful waiting.

Tumor growth is dependent on angiogenesis, which is thought to be controlled by angiogenic factors. Therefore, the immunoreactivity of the angiogenic cytokine vascular endothelial growth factor (VEGF) was semiquantitatively scored in archival prostate tumors obtained at diagnosis in 221 patients followed expectantly. At diagnosis, 125 patients suffered from clinically localized disease. Median length of follow-up was 15 years, and 57% of the patients eventually died of prostate cancer. All of the tumors exhibited cytoplasmic staining for VEGF. The staining intensity was weak in 47 tumors and moderate and strong in 107 and 67, respectively. VEGF expression was significantly correlated with microvessel density (MVD; median, 43; range, 16-151; P = 0.014), increasing T-classification (P = 0.001), dedifferentiation (P < 0.001), and disease-specific survival (P = 0.013). Strongly VEGF-immunoreactive, neuroendocrine-differentiated (NE) tumor cells were observed in 125 tumors. NE expression was significantly correlated with increasing MVD, increasing T-classification, dedifferentiation, and survival (all, P < 0.001). MVD and NE tumor cell expressions were significant variables in a multivariate analysis that included patients with clinically localized prostate cancer only. VEGF and NE expression were significantly correlated with MVD, clinical characteristics, and disease-specific survival. NE expression was a significant prognostic marker in localized prostate cancer patients, whereas the applied semiquantitatively scoring of VEGF expression was inadequate to make this growth factor provide any additional prognostic information. Moreover, the significant VEGF expression of NE tumor cells suggests an additional important character of these cells in the involvement in disease progression.     

Serum vascular endothelial growth factor (VEGF) levels correlate with tumor VEGF and p53 overexpression in endocrine positive primary breast cancer

Vascular endothelial growth factor (VEGF) is a potent stimulator of angiogenesis, associated with unfavorable clinical characteristics in breast cancer. The aim of this study was to evaluate different angiogenic markers in endocrine-positive breast cancer patients. The authors analyzed serum and tumor samples from 71 patients with endocrine-positive operable primary breast cancer to determine the expression and the possible relationship between circulating serum VEGF levels, tumor VEGF expression, microvessel density (MVD), and other immunohistochemical parameters. Basal VEGF serum levels were significantly higher in breast cancer patients than in healthy controls. A significant correlation was observed between basal VEGF serum concentrations, microvessel density (p = 0.01) and p53 status (p = 0.004). Intratumoral VEGF expression was significantly associated with neoplastic embolization (p = 0.041) and circulating VEGF levels (p = 0.047). The results confirm that in primary endocrine-positive breast cancer serum VEGF levels are elevated and show a positive relationship with tumor VEGF and p53 overexpression.     

早期三阴性乳腺癌与非三阴性乳腺癌VEGF和MVD表达的比较

目的探讨血管内皮生长因子（vascularendothelialgrowthfactor,VEGF）、微血管密度（microvesseldensity,MVD）在早期三阴性乳腺癌组织中与非三阴性乳腺癌组织中的表达水平。方法采用免疫组化染色法检测我院2007年1～12月行根治性手术切除、经病理证实的乳腺癌组织蜡块89例（其中早期三阴性乳腺癌21例,非三阴性乳腺癌68例）癌组织中VEGF的表达及MVD值,分析VEGF的表达及MVD值在早期三阴性乳腺癌和非三阴性乳腺癌组织中的差别,以及VEGF和MVD之间的关系。结果早期三阴性乳腺癌癌组织中VEGF表达的阳性率高于非三阴性乳腺癌（71．43％vs25．00％,P〈O．001）。MVD在早期三阴性乳腺癌与非三阴性乳腺癌组间的差异无统计学意义（P=0．105）。结论VEGF表达与乳腺癌血管生成密切相关,VEGF及MVD在三阴性乳腺癌中的生物学意义值得进一步探讨。     

新辅助化疗后乳腺癌患者VEGF、MVD、Neu基因观察及预后的研究

目的 :探讨新辅助化疗后乳腺癌患者血管内皮生长因子 (VEGF)、微血管密度 (MVD)及癌基因 (c erbB 2 /Neu)有否变化及与预后的关系。方法 :选择确诊为乳腺癌的患者 33例 ,检测经动脉新辅助化疗后VEGF及Neu基因的表达及MVD。同期设未行化疗的乳腺癌患者 35例为对照组。结果 :化疗后患者MVD与对照组差异有显著意义 ,P <0 0 5。观察组与对照组患者Neu基因阳性表达分别为 4 8% (2 1/33)、5 1%(18/35 ) ,差异无显著意义。观察组与对照组的VEGF阳性表达分别为 5 2 % (17/33)、4 9% (17/35 ) ,差异无显著意义。化疗组VEGF表达阳性者的MVD高于阴性患者 ,但无相关性 ,r =0 2 7,P >0 0 5 ;对照组VEGF表达阳性者的MVD高于阴性患者 ,VEGF与MVD呈正相关性 ,r =0 38,P <0 0 5 ;术前化疗组乳腺癌患者 3年内复发 5例 ,未行术前化疗乳腺癌患者 3年内复发 13例 ,复发者其MVD明显高于未复发者 ,且复发者Neu基因均为阳性表达 ,差异有显著意义 ,P <0 0 5。结论 :新辅助化疗可以降低MVD ;MVD及Neu基因的高表达可作为判断乳腺癌患者预后的重要指标。新辅助化疗可以降低肿瘤患者术后复发率与MVD减少有关 ,对于估计肿瘤患者预后及指导临床治疗具有重要意义     

乳腺癌组织中IL-8和MVD的表达与预后关系

目的:检测乳腺癌组织中IL-8和微血管密度(microvessel density,MVD)表达,探讨其与临床病理学因子及生物学因子的关系。方法:采用免疫组化SP法检测乳腺癌组织中IL-8、ER、PR、VEGF和CD105的表达。结果:1)103例乳腺癌组织中,IL-8阳性表达率为79.6%(82/103),正常及良性组织IL-8阳性率为13.8%(4/29),两者相比差异有统计学意义,P=0.000。2)MVD计数值范围为0~17.67,中位数为5.33。3)IL-8与VEGF和MVD表达均呈现正相关性,rs值分别为0.332和0.425,P值均为0.000。4)IL-8与淋巴结转移及临床分期有关,P值分别为0.002和0.024。5)IL-8与ER、PR、肿瘤大小及病理类型无关,P值分别为0.449、0.467、0.921和0.145。6)IL-8表达和MVD与乳腺癌预后有关,P值分别为0.006和0.002。结论:IL-8表达和MVD与影响乳腺癌患者预后的生物学因素相关,IL-8和MVD高表达,预后差,可作为判断乳腺癌预后指标。     

乳腺癌组织VEGF和p120表达及其临床意义的探讨

目的:观察血管内皮生长因子(VEGF)及连环蛋白p120在乳腺腺病和乳腺癌中的表达,探讨两者与乳腺癌临床病理特征的临床意义.方法:采用免疫组化SP法检测62例乳腺癌及26例乳腺腺病组织中VEGF和p120的表达情况.结果:乳腺癌组织中VEGF和p120的异常表达率分别为77.4％(48/62)和80.6％(50/62),与良性组相比差异有统计学意义,P=0.000.两者均与肿瘤病理分级和TNM分期相关,但均与肿瘤大小无相关.VEGF在有腋窝淋巴结转移 的癌组织中阳性率明显高于无淋巴结转移者,P=0.017,p120表达情况和淋巴结转移无关,P=0.072.两者在乳腺癌组织中的表达具有正相关性,P=0.011.结论:VEGF及p120在乳腺癌组织中异常表达,并与乳腺癌浸润转移关系密切,是乳腺癌发生发展的生物学指标之一,联合检测对评估预后及临床治疗有指导意义.     

Serum VEGF levels in women with a benign breast tumor or breast cancer

Vascular endothelial growth factor (VEGF) is an important regulator of angiogenesis and vascular permeability. Many types of malignant human tumors have been shown to produce VEGF. Recently, increased serum concentrations of VEGF (S-VEGF) have been reported in patients with various types of cancer, and high S-VEGF levels have also been associated with unfavorable prognosis. We have now measured S-VEGF in sera taken from 105 patients with a benign breast tumor or breast cancer. None of the women with a benign breast tumor had S-VEGF higher than 328 pg/ml (median, 57 pg/ml) whereas S-VEGF levels in metastatic breast cancer ranged from 7 to 1347 pg/ml (median, 186 pg/ml P=0.0018), and in locoregional breast cancer from 11 to 539 pg/ml (median, 104 pg/ml P=0.13). S-VEGF was higher in patients with locoregional ductal cancer (median, 107 pg/ml) than in those with locoregional lobular cancer (median, 44 pg/ml; P=0.029) or in patients with benign breast tumor (median, 57 pg/ml; P=0.033). Patients with metastatic cancer undergoing therapy had lower S-VEGF than those who had symptomatic treatment only (P=0.021). The results indicate that dissemination of breast cancer may be accompanied by an elevation of circulating VEGF and that primary ductal cancers are associated with higher S-VEGF levels than lobular cancers or benign breast lesions.     

RECK、VEGF和MVD在非小细胞肺癌中的表达及其相关性

[目的]探讨RECK与血管内皮生长因子(VEGF)、微血管密度(MVD)在非小细胞肺癌(NSCLC)中的表达和相关性.[方法]采用免疫组化SP法检测80例肺癌组织和20例癌旁正常肺组织中RECK、VEGF和MVD的表达水平.[结果]NSCLC中RECK的表达低于癌旁组织(36.25％vs 85.00％,P=0.0001),VEGF(68.75％vs 35.00％,P=0.005)和MVD(20.94±8.76 vs 10.57±4.24,P=0.0001)的表达高于癌旁组织.RECK表达在鳞癌和中、低分化的肿瘤中降低;VEGF在腺癌中表达增高;MVD值在年龄小于60岁患者中增高.VEGF表达与MVD呈正相关;RECK表达与MVD呈负相关.多变量Logistic回归分析显示RECK蛋白表达下调是NSCLC预后不良因素.[结论]RECK、VEGF、MVD表达在NSCLC中有一定相关性,RECK低表达是NSCLC独立不良预后因素.     

非小细胞肺癌患者血清IL-17和VEGF含量的检测及其临床意义

目的检测非小细胞肺癌non—smallcelllungcancer,NSCLC）患者血清中自细胞介素17（interleukin．17,IL．17）和血管内皮生长因子vascularendothelialgrowthfactor,VEGF）的含量并分析其临床意义。方法采用双抗体夹心酶联免疫吸附法（ABC．ELISA）检测52例NSCLC患者术前血清和26名健康体检者血清中IL-17和VEGF的水平,比较两组血清中IL-17和VEGF含量水平的差异,并分析其与临床病理特征的关系。结果52例NSCLC血清中IL-17和VEGF的含量均明显高于26名健康志愿者（P=0．000）。NSCLC患者血清中IL-17和VEGF的含量呈负相关（r=-0．88,P=0．000）。NSCLC患者血清中IL-17的水平与吸烟状态、病理类型和临床分期相关,其中吸烟人群高于非吸烟人群（P=O．048）,鳞癌高于腺癌（P=0．001）,随着临床分期的增加,IL-17的水平逐渐降低。NSCLC患者血清中VEGF的水平与分化程度、临床分期相关,其中低分化患者高于中高分化者（P=0．000）,且VEGF的水平随临床分期的增加而逐渐升高。结论NSCLC患者血清中IL-17和VEGF的水平均升高,两者均与临床病理特征密切相关,检测血清中IL-17和VEGF的水平对判断NSCLC患者的疾病状态有一定的参考价值。     

乳腺癌组织中MT1-MMP、VEGF的表达及其相关性

目的 探讨MT1-MMP和VEGF在乳腺癌组织中的表达及其与乳腺癌临床病理特征间的关系.方法 采用免疫组织化学方法检测67例乳腺癌组织和癌旁正常组织中MT1-MMP和VEGF的表达情况,并与临床病理特征进行相关性分析.结果 MT1-MMP和VEGF在乳腺癌组织中的表达水平显著高于在癌旁正常组织中的表达水平（P＜0.05）.VEGF 和MT1-MMP在乳腺癌组织中的表达呈正相关（P=0.005）.VEGF的表达与乳腺癌的TNM分期和淋巴结转移相关（P＜0.05）;MT1-MMP表达与乳腺癌的TNM分期和腋窝淋巴结转移相关（P＜0.05）.结论 MT1-MMP和VEGF的过表达与乳腺癌的浸润转移有关,二者联合检测对判断乳腺癌的恶性程度和预后具有重要价值.     

乳腺癌血管内皮生长因子的表达及意义

目的探讨血管内皮生长因子（VEGF）在乳腺癌中的表达及其与血管生成，肿瘤转移等参数之间的关系。方法对101例浸润性乳腺癌组织的VEGF表达进行了免疫组化检测。结果正常乳腺组织及良性病变组织均无VEGF表达。乳腺癌VEGF表达与组织分化（P＜0．05），淋巴结转移（P＜0．005），远处转移（P＜0．005）及早期死亡（P＜0．005）密切相关，与乳腺癌组织微血管密度（MVD）亦呈显著相关性（P＜0．05）；与患者年龄，肿瘤大小无关（P＞0．05）。结论VEGF是促进乳腺癌血管生成的主要因素。VEGF阳性的乳腺癌组织分化差，易发生转移，预后不良。     

肺癌患者血清中血管内皮生长因子的表达及其临床意义

目的:采用ELISA法检测肺癌患者血清血管内皮生长因子（VEGF）含量变化,以探讨其改变与肺癌临床诊断以及预后的关系。方法:原发性肺癌患者50例,取空腹静脉血4ml,采用酶联免疫吸附法(ELISA)测定血清中VEGF的水平,同时检测肺良性病变及健康体检者各50例,分别作为良性对照组及健康对照组。结果:肺癌组VEGF表达水平明显高于肺良性疾病组和健康对照组,有统计学意义（P＜0.05）;小细胞肺癌高于非小细胞肺癌,淋巴结转移者高于无转移者,差异均显著（P＜0.05）;且依TNM分期的早晚呈上升趋势,即:VEGF水平Ⅳ期＞Ⅲ期＞Ⅱ期＞Ⅰ期,组间差异显著（P＜0.05）;而血清VEGF水平与患者生存期呈负相关(r=-0.38,P＜0.05)。结论:检测肿瘤患者血清中VEGF的水平变化,对于肺癌的诊断和预后具有重要意义。     

Plasma VEGF concentration can predict the tumor angiogenic capacity in non-small cell lung cancer

We assessed the clinical utility of circulating angiogenic factors as a predictor for tumor angiogenesis in primary lung cancer. Circulating vascular endothelial growth factor (VEGF) and intratumoral VEGF were assessed by enzyme-linked immuno-sorbent assay (ELISA). There was a significant increase in the mean value of both plasma and serum VEGF concentration in primary lung cancer patients (n=97) compared to those of healthy controls (n=59). There was a significant correlation between plasma VEGF levels and microvessel density (MVD), and also between plasma VEGF and intratumoral VEGF levels. Plasma VEGF in patients with lung cancer appears to be a useful indicator of tumor angiogenesis.     

乳腺癌组织中VEGF的表达及临床意义

目的 研究血管内皮生长因子(vascular endothelial growth factor,VEGF)在乳腺癌中的表达及临床意义.方法 应用免疫组织化学S-P法检测52例乳腺癌组织和18例乳腺良性病变中VEGF的表达情况,结合临床及病理形态学资料进行统计分析.结果 VEGF正常乳腺组织中阳性表达率低于乳腺癌组织的阳性表达率(P＜0.05).VEGF在腋淋巴结阳性组和复发/远处转移组的阳性率明显高于腋淋巴结阴性组和未发生远处转移/复发组(P＜0.05);乳腺癌VEGF表达与ER(P＜0.05)、PR(P＜0.05)、生存期(P＜0.05)呈负相关;与CerbB-2(P＜0.05)、临床分期(P＜0.05),呈正相关.VEGF与患者年龄、肿块大小无显著性差异(P＞0.05).结论 VEGF可能与乳腺癌的进展、转移及预后有关,作为独立的指标对判定预后和制定治疗方案具有参考意义.