VEGF和CD31在子宫内膜样腺癌中的表达及其临床意义

目的:检测血管内皮生长因子(VEGF)和CD31在不同子宫内膜组织中的表达情况。方法:采用免疫组化方法检测VEGF、CD31在52例子宫内膜样腺癌组织、22例子宫内膜不典型增生组织及21例正常子宫内膜组织中的表达,对结果进行量化分析。结果:(1)VEGF在正常子宫内膜组织、不典型增生组织及子宫内膜样腺癌中表达的阳性率分别为23.8%、31.8%、65.4%;CD31在正常子宫内膜组织、不典型增生组织及子宫内膜样腺癌组织中标记的微血管密度(microvessel density,MVD)分别为23.6±11.7、31.5±17.7、51.9±21.1。VEGF的阳性表达及CD31-MVD(CD31标记的MVD)在子宫内膜样腺癌组织中明显高于不典型增生及正常子宫内膜组织(P0.05)。(2)VEGF在子宫内膜样腺癌中的表达,与淋巴结转移有关(P0.05)。CD31-MVD与肿瘤分期、浸润肌层深度、组织学类型有关(P0.05)。(3)在子宫内膜样腺癌组织,VEGF表达与CD31-MVD无明显相关性(r=0.095,P=0.504)。结论:VEGF表达、CD31-MVD在子宫内膜样腺癌组织中增高,可能促进子宫内膜样腺癌的发生发展及转移浸润。     

分化抑制因子Id-1与VEGF及MVD在宫颈癌变中的相关性分析

目的:研究分化抑制因子-1(Id-1)与血管内皮生长因子(VEGF)及微血管密度(MVD)在宫颈组织癌变中的相关性,探讨Id-1在宫颈癌血管形成中的机理。方法:采用免疫组化法检测50例宫颈癌石蜡标本中Id-1、VEGF及CD34的表达;用CD34标记肿瘤微血管,计算MVD。结果:宫颈癌组织中Id-1、VEGF及MVD均呈高表达,且均与临床FIGO分期进展具有相关性(P<0.05)。宫颈癌组织中三者的表达具有显著正相关性(P<0.01),Id-1与VEGF、Id-1与MVD的spearman相关系数(Ra)分别为0.43,0.48。结论:宫颈癌组织中Id-1与VEGF、MVD的表达具有正相关性,Id-1可能是通过促进肿瘤微血管生成的机制参与宫颈癌的发生。     

卵巢上皮性肿瘤组织中血管内皮生长因子的表达及与微血管密度相关性研究

目的探讨卵巢上皮性肿瘤组织中血管内皮生长因子(VEGF)的表达、微血管密度(MVD)及其与临床病理因素的关系.方法 2000年7月至2003年7月哈尔滨医科大学第一临床医学院采用免疫组化方法检测30例恶性卵巢上皮性肿瘤、30例良性卵巢上皮性肿瘤中VEGF和MVD的表达,分析其相关性及与卵巢上皮性肿瘤临床病理因素之间的关系.结果 60例卵巢上皮性肿瘤中,VEGF在恶性卵巢上皮性肿瘤中的表达阳性率为80.00%,MVD为26.43±10.40,显著高于良性卵巢上皮性肿瘤组织VEGF的表达率(36.67%)及MVD值4.11±2.31.VEGF表达阳性的恶性卵巢上皮性肿瘤组织的MVD值显著高于VEGF表达阴性者(P<0.05);VEGF阳性表达与MVD值呈正相关.有淋巴结转移的恶性卵巢上皮性肿瘤组织中,VEGF表达与MVD值显著高于无淋巴结转移者,而与手术临床分期、病理分级及组织学类型无相关性(P＞0.05).结论 VEGF与卵巢上皮性肿瘤的生长及转移有关,并可能成为卵巢癌临床生物学治疗的参考指标.     

宫颈鳞癌微血管密度血管内皮生长因子表达意义的研究

目的探讨宫颈鳞癌微血管密度、血管内皮生长因子(VEGF)蛋白表达在判断肿瘤生物学行为中的意义,以期为宫颈癌的预后评估和指导临床治疗提供新的依据.方法应用免疫组织化学SP法检测宫颈癌组织中微血管密度、VEGF蛋白表达,分析其与肿瘤组织学分级、临床分期及它们相互之间的关系,并分别研究其与预后的关系.结果宫颈鳞癌微血管密度、VEGF蛋白表达与肿瘤组织学分级、临床分期无关;VEGF阳性组微血管密度明显高于阴性组(P＜0.01).微血管密度较高组的存活率低于微血管密度较低组(P＜0.01),VEGF表达对存活率无明显影响(P＞0.05).结论宫颈鳞癌VEGF阳性组微血管密度高于阴性组,说明VEGF有促进宫颈鳞癌血管形成的作用.癌组织中微血管密度与预后有关,提示肿瘤微血管化的评估可能会成为一种新的预测宫颈鳞癌预后的手段.     

新辅助化疗对宫颈癌微血管密度及血管内皮生长因子的影响

目的 :研究进展期宫颈癌新辅助化疗 (NACT)前后微血管密度 (MVD)及血管内皮生长因子 (VEGF)的改变 ,探讨新辅助化疗对宫颈癌治疗的意义。方法 :手术前行NACT的宫颈癌患者 37例为研究组 (NACT组 ) ,直接手术的 2 0例患者为对照组。应用免疫组化方法检测宫颈癌组织的MVD和VEGF的表达 ,分析其改变与NACT的关系和意义。结果 :(1 )NACT的总有效率为 62 .2 % ;(2 )NACT组在化疗前与直接手术组MVD和VEGF的表达差异无显著性 ;(3)NACT有效者的MVD和VEGF的表达明显降低 ,无效者则无明显变化 ;(4)NACT后宫颈腺癌和鳞癌的MVD和VEGF表达率无显著差异。结论 :NACT对进展期宫颈癌有效 ,NACT有效者的MVD和VEGF表达明显减低 ,MVD和VEGF可以作为NACT的客观评价新指标     

宫颈癌中环氧合酶2与血管内皮生长因子C的表达及相关研究

目的:探讨环氧合酶2(COX-2)和血管内皮生长因子C(VEGF-C)在宫颈癌中的表达及意义.方法:应用免疫组织化学S-P法检测42例宫颈癌、20例宫颈上皮内瘤样变(CIN I-Ⅲ)、10例正常宫颈组织中COX-2和VEGF.C的表达.结果:宫颈癌组COX-2和VEGF-C阳性表达率分别高于CIN组及正常官颈组(P<0.05).不同年龄、预后COX-2表达无差异(P>0.05),但不同病理类型和临床分期间表达差异有统计学意义(P<0.05).不同年龄、病理类型、预后VEGF-C表达无差异(P>0.05),但不同临床分期间表达差异有统计学意义(P<0.05).COX-2和VEGF-C在宫颈癌组织中的表达呈正相关(r=0-4l.P(0.05).结论:COX-2和VEGF-C在宫颈癌的发生发展中起重要作用.可能作为宫颈癌早期诊断和判断预后的重要指标.     

宫颈癌中血管内皮生长因子、环氧合酶-2的表达及意义

目的　探讨环氧合酶 - 2 (COX - 2 )在宫颈癌中的表达 ,及其与血管内皮生长因子 (VEGF)表达和肿瘤微血管密度 (MVD)的关系。方法　应用免疫组化法检测 5 4例宫颈癌中COX - 2、VEGF的表达和MVD值 ,并以 1 0例宫颈CIN和 1 0例正常宫颈上皮为对照组。结果　宫颈癌中COX - 2阳性表达率分别为Ⅰ期5 6 7%、Ⅱ期为 6 6 7%、Ⅲ期 77 8%。VEGF在宫颈癌中阳性表达率分别为Ⅰ期 76 7%、Ⅱ期 80 0 % ,Ⅲ期88 9%。COX - 2在宫颈癌Ⅰ、Ⅱ、Ⅲ期间差异无显著性 (P >0 0 5 )。VEGF宫颈癌Ⅰ、Ⅱ期间差异无显著性 (P>0 0 5 ) ,Ⅰ期与Ⅲ期之间差异有显著性 (P <0 0 5 )。COX - 2、VEGF与MVD的表达呈正相关 ,而与不同的病理分级无明显相关性 (P >0 0 5 )。结论　VEGF、COX - 2、MVD在宫颈癌的发生、发展过程中起着重要作用 ,VEGF、COX - 2、MVD值可作为检测指标 ,为宫颈癌的诊断、临床分期及治疗起指导作用     

宫颈鳞癌组织C-Fos、PDGFR蛋白的表达及意义北大核心CSCD

目的探讨宫颈鳞癌组织C-Fos、PDGFR蛋白的表达及意义。方法选取2015年1月至2017年10月河北省承德医学院附属医院保存的宫颈癌组织58例,宫颈上皮内瘤变(CIN)组织47例,正常宫颈组织43例,采用免疫组化染色检测C-Fos、PDGFR蛋白阳性表达,western blot检测C-Fos、PDGFR蛋白表达量。结果宫颈癌组织C-Fos和PDGFR蛋白阳性表达率分别为58.62%和62.07%,C-Fos和PDGFR蛋白表达量分别为(0.987±0.221)和(0.872±0.206),明显高于CIN和正常宫颈组织(P <0.05);CIN组织C-Fos和PDGFR蛋白阳性表达率分别为21.28%和27.66%,C-Fos和PDGFR蛋白表达量分别为(0.344±0.157)和(0.550±0.214),明显高于正常宫颈组织(P <0.05);Ⅲ～Ⅳ期宫颈癌C-Fos和PDGFR蛋白表达量分别为(1.012±0.220)和(1.012±0.220),明显高于Ⅰ～Ⅱ期宫颈癌(P <0.05);中低分化宫颈癌PDGFR蛋白表达量为(0.892±0.184),明显高于高分化宫颈癌(P <0.05);宫颈癌组织C-Fos和PDGFR蛋白表达量无相关性(P>0.05)。结论宫颈鳞癌组织C-Fos、PDGFR蛋白表达明显高于CIN和正常宫颈,与临床分期和分化程度具有一定的相关性,可能在宫颈癌发生过程中发挥一定的作用。     

宫颈鳞癌组织C-Fos、PDGFR蛋白的表达及意义

目的探讨宫颈鳞癌组织C-Fos、PDGFR蛋白的表达及意义。方法选取2015年1月至2017年10月河北省承德医学院附属医院保存的宫颈癌组织58例,宫颈上皮内瘤变(CIN)组织47例,正常宫颈组织43例,采用免疫组化染色检测C-Fos、PDGFR蛋白阳性表达,western blot检测C-Fos、PDGFR蛋白表达量。结果宫颈癌组织C-Fos和PDGFR蛋白阳性表达率分别为58.62%和62.07%,C-Fos和PDGFR蛋白表达量分别为(0.987±0.221)和(0.872±0.206),明显高于CIN和正常宫颈组织(P 0.05);CIN组织C-Fos和PDGFR蛋白阳性表达率分别为21.28%和27.66%,C-Fos和PDGFR蛋白表达量分别为(0.344±0.157)和(0.550±0.214),明显高于正常宫颈组织(P 0.05);Ⅲ～Ⅳ期宫颈癌C-Fos和PDGFR蛋白表达量分别为(1.012±0.220)和(1.012±0.220),明显高于Ⅰ～Ⅱ期宫颈癌(P 0.05);中低分化宫颈癌PDGFR蛋白表达量为(0.892±0.184),明显高于高分化宫颈癌(P 0.05);宫颈癌组织C-Fos和PDGFR蛋白表达量无相关性(P0.05)。结论宫颈鳞癌组织C-Fos、PDGFR蛋白表达明显高于CIN和正常宫颈,与临床分期和分化程度具有一定的相关性,可能在宫颈癌发生过程中发挥一定的作用。     

VEGF、P53在卵巢上皮性肿瘤的表达及其与血管生成关系的研究

目的探讨VEGF、P53在卵巢上皮性肿瘤中的表达及其与血管生成的关系,旨在了解卵巢上皮性肿瘤血管生成活性及其调节机制,为卵巢癌的治疗提出新的思路.方法采用免疫组化LSAB法分析74例卵巢上皮性肿瘤微血管密度(MVD)、血管内皮生长因子(VEGF)和P53蛋白的表达状况及三者间的关系.结果MVD在腺瘤、交界瘤、卵巢癌中的数值依次升高,各组间差异均有显著性(P＜0.001,P＜0.05);MVD在卵巢癌中粘液性明显高于浆液性和子宫内膜样(P＜0.05,P＜0.05);VEGF在卵巢癌中的表达率明显高于腺瘤及交界瘤(P＜0.05).P53蛋白仅出现于卵巢癌组织,表达率50%,卵巢癌P53蛋白阳性组MVD高于P53阴性组(P＜0.05);等级相关分析显示卵巢上皮性肿瘤VEGF的表达强度与MVD呈正相关(r=0.762,P＜0.001);P53、VEGF间也存在正相关关系(ra=0.762,P＜0.01).结论血管生成活性的不同,有助于卵巢良、恶性肿瘤的鉴别;VEGF是卵巢上皮性肿瘤重要的促血管生成因子,且可能与卵巢癌腹水形成有关;P53突变可促进卵巢上皮性癌的血管生成,且在一定程度上可上调VEGF表达.     

子宫内膜增生过长和子宫内膜样腺癌中VEGF 和TSP-1表达与血管新生研究

目的探讨子宫内膜增生过长及子宫内膜样腺癌中血管内皮生长因子(VEGF)和血小板反应素1(TSP-1)表达与血管新生的关系以及对子宫内膜样腺癌的发生、发展中的作用.方法采用免疫组织化学方法分别检测子宫内膜正常(12例)、增生过长(13例)、不典型增生(18例)及子宫内膜样腺癌(50例)中微血管密度(MVD)、VEGF及TSP-1表达情况.结果子宫内膜不典型增生和内膜样腺癌中MVD明显大于内膜正常及增生过长者(P＜0.05),子宫内膜样腺癌IA期与不典型增生二者的MVD差异无显著性(P＞0.05),而与正常内膜和增生过长者差异有显著性(P＜0.05);VEGF表达与上述不同内膜病变中MVD呈正相关(r=0.843,P=0.000 1),而TSP-1表达仅在子宫内膜样腺癌中分别与MVD和VEGF呈负相关趋势(r=-0.233,P=0.1041;r=-0.235,P=0.100 3);在子宫内膜样腺癌中TSP-1间质高表达且具有异质性.结论子宫内膜不典型增生和子宫内膜样腺癌中VEGF对血管新生起正向调节作用;TSP-1在部分腺癌患者中表达增强,但其负向调节作用较弱,可能会使血管新生开关平衡失调,与子宫内膜样腺癌发生及发展有关.     

Expression of vascular endothelial growth factor in adenocarcinomas of the uterine cervix and its relation to angiogenesis and p53 and c-erbB-2 protein expression

OBJECTIVE: The purpose of this study was to evaluate vascular endothelial growth factor (VEGF) expression in adenocarcinomas of the uterine cervix and its correlation with clinicopathologic features, angiogenesis, and expression of p53 and c-erbB-2 proteins. METHODS: Thirty-seven cases of FIGO clinical stage I and II adenocarcinoma of the uterine cervix were examined by immunohistochemical studies with anti-VEGF, anti-CD34, anti-p53, and anti-c-erbB-2 antibodies. Computerized image analysis was used to evaluate microvessel density (MVD). RESULTS: Thirty-one tumors (83.8%) were classified as VEGF positive. Six tumors (16.2%) showed p53 protein expression while 11 tumors (29.7%) expressed the c-erbB-2 protein. MVD ranged from 13.3 to 44.8, with a median value of 25.5 (26.9 +/- 7.5). Tumors expressing VEGF had a significantly higher MVD than those that did not express VEGF (P < 0.05). VEGF expression was significantly associated with c-erbB-2 protein expression (P < 0.05). The spatial distributions of both VEGF expression and c-erbB-2 expression were similar in tumor tissues. In univariate log-rank analysis, stage (P = 0.0250), lymphovascular space invasion (P = 0.0156), and MVD (P = 0.0360) were associated with shortened survival. CONCLUSION: VEGF expression plays a role in promoting angiogenesis in cervical adenocarcinomas and c-erbB-2 is likely to be involved in the up-regulation of VEGF expression.     

分化抑制因子-1在宫颈癌组织中表达及其与微血管密度的关系

目的探讨分化抑制因子-1(Id-1)在宫颈癌组织中的表达及其与肿瘤发生、发展以及血管生成的关系。方法 2009年2月至2010年6月在吉林大学第二临床医院采用免疫组化法检测35例宫颈浸润癌(ICC)组织及20例正常宫颈上皮组织(NCE)中Id-1和微血管密度(MVD)的表达。结果 Id-1蛋白在宫颈癌组织中阳性表达率为71.43%,正常宫颈上皮组织中阳性表达率为0,两组比较有统计学意义(P<0.01),ICC组Id-1高表达与组织分化程度、间质浸润深度和盆腔淋巴结转移相关(P﹤0.05),而与FIGO分期无关(P﹥0.05);MVD计数在宫颈癌组织中表达为46.57±10.291,在正常宫颈上皮组织中为12.40±3.761,两组比较有统计学意义(P<0.05),MVD的表达在ICC组内与盆腔淋巴结转移、组织分化程度有关(P﹤0.05),而与FIGO分期、间质浸润深度无关(P﹥0.05);ICC组中Id-1表达强度与MVD呈正相关(r=0.648,P﹤0.01)。结论 Id-1因子通过促进肿瘤血管生成,从而参与宫颈癌的发生发展;子宫颈癌组织中的MVD值随着Id-1因子表达强度的增加而增高。阻断Id-1因子在子宫颈癌中的表达,有望成为治疗宫颈癌的途径之一。     

Angiogenesis in malignancies of the female genital tract

OBJECTIVE: The purpose of this work was to review current knowledge pertaining to angiogenesis in malignancies of the female genital tract. METHODS: We identified studies published in the English language regarding angiogenesis in gynecologic malignancies. The studies were obtained from a MEDLINE search from 1966 through June 1998; additional sources were identified through cross-referencing. RESULTS: A growing body of evidence confirms the ability of vulvar and cervical squamous cell carcinomas and endometrial and ovarian adenocarcinoma to induce angiogenesis. In vulvar intraepithelial neoplasia a correlation between vascular endothelial growth factor (VEGF) expression, microvessel density (MVD), and progression of dysplasia has been demonstrated. In invasive vulvar carcinoma, high VEGF expression and MVD portend poor prognosis. Currently a debate exists regarding the ability of cervical squamous intraepithelial neoplasia to induce angiogenesis. Most studies, however, indicate angiogenesis to be of prognostic value in patients with invasive squamous cell carcinoma. The ability of complex endometrial hyperplasia to induce angiogenesis has been demonstrated. A direct correlation between angiogenesis, higher grade and depth of invasion in Stage I adenocarcinoma, and prognostic value in Stage I and II and recurrent disease has been noted. In ovarian epithelial adenocarcinoma, higher microvessel counts in the primary ovarian tumor or omental metastases may serve as a prognostic indicator for survival. CONCLUSIONS: Similar to other malignant diseases, angiogenesis appears to play an important role in disease progression and survival in patients with gynecologic malignancies. Preliminary data indicate angiogenesis may serve as a prognostic indicator in vulvar and cervical squamous cell carcinomas and endometrial and ovarian adenocarcinomas. These findings may lead to future application of therapeutic trials with antiangiogenic factors.     

Hypoxia-stimulated expression of angiogenic growth factors in cervical cancer cells and cervical cancer-derived fibroblasts

Abstract. Pilch H, Schlenger K, Steiner E, Brockerhoff P, Knapstein P, Vaupel P. Hypoxia-stimulated expression of angiogenic growth factors in cervical cancer cells and cervical cancer-derived fibroblasts.
It is generally accepted that local growth of solid tumors and their ability to establish distant metastases are dependent on the formation of new blood vessels arising from preexisting ones (angiogenesis). The angiogenic response of the host is mediated by angiogenic molecules that are released from cancer and normal stroma cells, especially fibroblasts. The goal of the present study was to quantitatively compare the expression of the two most important angiogenic growth factors (VEGF, angiogenin) of cervical cancer cells (HeLa and Me-180) with that of cervical cancer-derived fibroblasts (from one tumor/patient) under defined normoxic and hypoxic conditions in vitro .
The growth kinetics of cervical cancer cells (HeLa and Me-180) and tumor-derived fibroblasts were evaluated in vitro under normoxic and hypoxic conditions. Growth factor concentrations in the cell culture medium were measured by ELISA and the secretion rates per cell were calculated. Under normoxic conditions, both the cervical cancer cells as well as the tumor-derived fibroblasts released VEGF and angiogenin. The secretion rate of both angiogenic factors was significantly higher in the stroma cells than in the tumor cells ( P < 0.05). VEGF and angiogenin secretion is significantly higher in the stroma cells under hypoxia than in the tumor cells investigated ( P < 0.05). The presented data support the concept that in cervical cancer non-neoplastic fibroblasts could play a pivotal role in the complex process of tumor angiogenesis.     

Expression of vascular endothelial growth factor and assessment of microvascular density with CD 34 and endoglin in proliferative endometrium, endometrial hyperplasia, and endometrial carcinoma

The aim of this study was to compare vascular endothelial growth factor (VEGF), CD 34, and endoglin expressions as markers of angiogenesis in proliferative endometrium (PE), endometrial hyperplasia (EH), and endometrial carcinoma (EC) and to find the possible impact of angiogenesis on malign transformation. Formalin-fixed, paraffin-embedded tissues from 12 patients with PE, 23 patients with simple EH and complex EH with atypia, and 31 patients with EC were included. A semiquantitative scoring system was used to assess the intensity and degree of staining of VEGF. Microvessel density (MVD) was assessed with endoglin and anti-CD 34 in most vascular areas. VEGF expression was significantly higher in EC and EH than PE, but there was no difference between EC and EH. According to CD 34 staining, there were no differences in MVD between groups. However, mean MVD counts assessed by endoglin were significantly higher in EC than PE and EH. Although VEGF expression in EC was significantly higher, it did not correlate with other measures of angiogenesis. MVD using endoglin seemed to reflect neoplastic angiogenesis better than CD 34.