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.     

应用组织芯片技术研究卵巢癌组织中缺氧诱导因子1α与血管生成的关系

目的　探讨缺氧诱导因子 1α(hypoxiainduciblefactor 1α ,HIF 1α)在卵巢癌组织中的表达及其与血管生成的关系。方法　联合应用组织芯片和原位杂交、免疫组化技术 ,检测 2 95份卵巢上皮性肿瘤 (其中卵巢癌 2 38份、交界性卵巢肿瘤 19份、良性卵巢肿瘤 38份 )及 13份正常卵巢组织中HIF 1αmRNA和血管内皮生长因子 (VEGF)的表达情况 ,以CD3 4 单克隆抗体标记血管内皮细胞来检测微血管密度 (MVD)。结果　卵巢癌、交界性卵巢肿瘤和良性卵巢肿瘤、正常卵巢组织中HIF 1αmRNA的阳性表达率分别为 81 9%、4 2 1%、13 2 %和 0。交界性卵巢肿瘤和卵巢癌组织中HIF 1αmRNA的表达高于正常卵巢和良性卵巢肿瘤 ,卵巢癌高于交界性肿瘤 ,差异均有统计学意义 (P <0 0 1)。卵巢癌组织中HIF 1αmRNA的表达与手术病理分期和病理类型无关 (P >0 0 5 ) ,而与病理分级呈正相关 (r=0 2 4 6 ,P <0 0 1)。卵巢癌组织中HIF 1αmRNA表达与VEGF表达 (r =0 2 0 6 ,P =0 0 1)和MVD计数 (r =0 4 5 1,P <0 0 1)均呈显著正相关。结论　卵巢癌组织过度表达HIF 1αmRNA ,并通过诱导VEGF促进肿瘤的新生血管形成。     

上皮性卵巢癌血管内皮生长因子的表达与肿瘤内微血管密度的相关性研究

目的 :探讨上皮性卵巢癌组织中血管内皮生长因子 (VEGF)是否与肿瘤内微血管密度 (MVD)、淋巴转移等临床病理学因素存在相关性。方法 :以多克隆抗VEGF抗体和单克隆抗CD34抗体分别标记 4 5例FIGOⅠ～Ⅳ期上皮性卵巢癌术后标本的VEGF和MVD。用彩色图像病理分析系统测定VEGF的相对含量 ,MVD采用人工计数。分析VEGF与MVD、肿瘤期别、组织学类型、腹水量以及淋巴转移的关系。结果 :(1)VEGF的平均吸光度为 0 .178± 0 .14 9(中位数 0 .16 7)。MVD值平均为 72 .2 6± 5 8.5 2 /mm2 (中位数 6 8.4 7/mm2 ) ;(2 )VEGF表达水平与MVD之间存在显著相关性 (r =0 .92 6 ,P <0 .0 1) ;(3)盆腔淋巴转移(n =12 )VEGF平均吸光度 (0 .193± 0 .15 3)显著高于无盆腔淋巴转移组 (n =32 )的 0 .138± 0 .0 90 ,(P <0 .0 5 )。不同期别 ,组织学类型和腹水量之间的VEGF表达强度无显著差异(P >0 .0 5 )。结论 :VEGF表达与上皮性卵巢癌血管生成的增强密切相关     

宫颈癌血管内皮生长因子表达与血管生成癌细胞增殖及侵袭转移的关系

目的　研究血管内皮生长因子 (VEGF)在早期宫颈癌的表达和临床意义。方法　采用免疫组织化学SP法检测 1998年 1月至 2 0 0 2年 2月期间 75例早期宫颈癌 (ICC)、18例宫颈上皮内瘤样病变 (CIN)和 15例癌旁正常宫颈上皮 (NCE)中VEGF的表达情况 ,并检测其中微血管密度 (MVD ,CD3 4 标记 )和癌细胞增殖标记指数 (Ki 6 7标记 )。结果　从NCE→CIN→ICC ,VEGF、Ki 6 7的阳性表达率和MVD均显著升高 (P <0 0 5 )。VEGF在ICC的表达与MVD显著正相关 (r =0 6 0 2 ,P <0 0 1) ,与盆腔淋巴结转移、脉管浸润、组织学分级和Ki 6 7表达显著相关 (P <0 0 5 ) ,但与年龄、FIGO分期、组织学类型和间质浸润无关 (P >0 0 5 )。低分化、盆腔淋巴结转移、脉管浸润及Ki 6 7高度表达者 ,与VEGF阳性表达显著相关 (P <0 0 5 )。结论　VEGF阳性表达可能在宫颈癌血管生成、癌细胞增殖、癌细胞侵袭转移中起重要作用。VEGF检测对进一步了解宫颈癌生物学行为和判断其预后具有一定的临床应用价值。     

层粘连蛋白、基质金属蛋白酶-9在卵巢粘液性肿瘤中的表达及其意义

目的 :探讨层粘连蛋白 (LN)、基质金属蛋白酶 9(MMP 9)在卵巢粘液性肿瘤中的表达以及与临床病理因素和预后的关系。方法 :应用免疫组织化学方法检测 43例卵巢粘液性肿瘤LN、MMP 9的表达情况。结果 :LN、MMP 9的表达 ,在卵巢粘液性肿瘤从良性、交界性到恶性发展中 ,LN的表达级别和MMP 9的表达阳性率逐渐增高 ;LN的表达程度与卵巢粘液性囊腺癌的组织学分级有关 (P =0 0 0 0 ) ;MMP 9的表达与卵巢粘液性囊腺癌的组织学分级 (P =0 0 48)、FIGO分期 (P =0 0 47)、术后复发和死亡 (P =0 0 30 )有关。在卵巢粘液性囊腺癌中 ,LN的表达程度在MMP 9阳性组与MMP 9阴性组之间差异有显著性 (P =0 0 0 8) ,并呈正相关。结论 :LN、MMP 9在卵巢粘液性肿瘤的浸润转移中起重要作用 ,是卵巢粘液性肿瘤的恶性指标之一 ,可望作为交界性粘液性囊腺瘤及粘液性囊腺癌的诊断和分级的客观指标 ;MMP 9可协助临床估计预后。     

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。     

子宫颈鳞状细胞癌中TGF-β1表达与血管生成的关系

目的　研究转化生长因子 (transforminggrowthfactor - β1 ,TGF - β1 )在子宫颈鳞状细胞癌中的表达 ,及其与血管内皮生长因子 (VEGF)表达和肿瘤内微血管密度 (MVD)的关系。　方法　应用免疫组织化学方法检测 4 3例子宫颈鳞状细胞癌中TGF - β1、VEGF的表达和MVD值。 结果　子宫颈鳞状细胞癌中TGF - β1和VEGF阳性表达率分别为 34 9%和 6 2 8% ,MVD值为 1 7 2～ 1 1 4 6 ,平均值为 5 7 4 2± 2 3 1 5。TGF - β1的表达与肿瘤的淋巴结转移和临床分期密切相关 (P <0 0 5 ) ,而与肿瘤的病理分级无关 (P >0 0 5 ) ,TGF - β1表达与VEGF的表达呈正相关 (P <0 0 5 ) ,而与肿瘤的MVD无明显相关性 (P >0 0 5 )。结论　TGF - β1可能通过上调VEGF的表达间接刺激血管生成而促进子宫颈鳞状细胞癌的进展     

基质金属蛋白酶-9及基质金属蛋白酶组织抑制物-1表达失衡与宫颈癌局部肿瘤血管生成的关系

目的 :探讨基质金属蛋白酶 - 9(MMP 9)和基质金属蛋白酶组织抑制物 - 1(TIMP 1)在宫颈癌局部肿瘤血管生成中的作用。方法 :采用免疫组织化学SP法检测 75例早期宫颈癌 (ICC)、18例宫颈上皮内瘤样病变 (CIN)和 15例癌旁正常宫颈上皮 (NCE)中MMP 9和TIMP 1的表达情况 ,并检测其中微血管密度 (MVD ,CD3 4 标记 )。结果 :从NCE组到CIN组再到ICC组 ,MMP 9的阳性表达率显著升高 (P <0 0 5 )而TIMP 1未见升高 (P >0 0 5 ) ,并且TIMP 1在ICC组的阳性表达率显著低于MMP 9(P <0 0 1)。MMP 9在ICC组中表达与MVD显著正相关 (r =0 2 87,P <0 0 5 ) ,而TIMP 1与MVD无显著相关性 (r=0 195 ,P >0 0 5 )。宫颈癌中MMP 9表达高于TIMP 1者 ,其MVD显著高于MMP 9表达低于TIMP 1者 (P <0 0 5 )。结论 :MMP 9和TIMP 1表达失衡可能在宫颈癌局部肿瘤血管生成中起重要作用 ,MMP 9表达增强而TIMP 1表达降低 ,其血管生成能力可能显著增强 ,但并非唯一决定因素。检测宫颈癌中MMP 9和TIMP 1表达对进一步了解宫颈癌局部血管生成情况有一定的应用价值。     

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.     

VEGF、MMP-2、MMP-9在卵巢原发性与转移性癌中表达的研究

目的 :探讨VEGF、MMP 2、MMP 9在卵巢原发上皮癌、库肯勃氏瘤中的表达差异及临床病理意义。方法 :采用免疫组化S P染色技术对 83例卵巢癌 (卵巢原发癌 4 5例、库肯勃氏瘤 38例 )进行分析 ,观察VEGF、MMP 2、MMP 9在卵巢癌中的表达。结果 :VEGF在卵巢原发癌和库肯勃氏瘤组织中的表达显著高于正常卵巢组织 (P <0 .0 5 ) ;MMP 2、MMP 9在正常卵巢组织中表达缺如 ;VEGF、MMP 2、MMP 9在卵巢原发癌与库肯勃氏瘤中表达均有显著差异 (P <0 .0 5 ) ;VEGF、MMP 2、MMP 9在库肯勃氏瘤中及卵巢原发癌中 ,任意两指标阳性表达均有正相关性 (P <0 .0 5 )。结论 :VEGF、MMP 2、MMP 9在库肯勃氏瘤的形成机制中起重要作用 ,与肿瘤的浸润转移密切相关 ,并可为鉴别卵巢原发癌与库肯勃氏瘤提供一定的依据     

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.     

Prognostic significance of microvessel density and vascular endothelial growth factor expression in advanced ovarian serous carcinoma

The aim of the study was to test the prognostic value of the microvessel density (MVD) within the tumor and the vascular endothelial growth factor (VEGF) expression on clinical response to chemotherapy, on brief disease-free interval, and on cause-specific survival in advanced ovarian serous carcinoma. We evaluated 83 ovarian carcinomas homogeneous for stage, type and grade histologic, surgical, and chemotherapeutic treatment. Brief disease-free interval and cause-specific survival rates (Kaplan-Meier method) were compared using the log-rank test. A multivariate analysis (Cox-proportional hazards model) was used to determine the independent effect of each variable on prognosis. Overall 60 and 120 months cause-specific survival rates were 27.7% and 2.4%, respectively. The brief disease-free interval rate was 66.2%. In univariate analysis, VEGF (P = 0.0001 and P = 0.016), MVD (P < 0.0005), and the FIGO stage IIIC even more than FIGO stage IIIA (P = 0.01 and P < 0.0005, respectively) were associated with survival and brief disease-free interval, and the residual tumor was associated with survival (P = 0.021). In multivariate analysis, the factors that were independent predictors of survival were MVD (P < 0.0005), VEGF (P = 0.027), and the FIGO stage IIIC even more than FIGO stage IIIA (P = 0.013). Moreover, MVD was an independent predictor also of brief disease relapse (P = 0.001). Both MVD and VEGF were correlated with clinical response to chemotherapy (P = 0.01 and P = 0.037). Our data suggest that MVD and VEGF may have prognostic significance in advanced ovarian serous carcinoma.     

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。     

不同级别卵巢浆液性癌中E-cadherin和p120蛋白的表达及意义

目的:探讨上皮性钙黏附蛋白(E-cadherin)和连环蛋白p120在不同组织学级别卵巢浆液性癌中的表达及意义。方法:用免疫组化EnVision二步法,分别检测31例卵巢低级别浆液性癌和70例卵巢高级别浆液性癌中E-cadherin和p120蛋白的表达水平,分析其与卵巢浆液性癌临床病理资料的相关性。结果:E-cadherin在低级别浆液性癌和高级别浆液性癌中的阳性率分别为71.0%和61.4%(P=0.356);p120的阳性率分别为83.9%和60.0%(P=0.018)。高级别浆液性癌中,E-cadherin和p120蛋白表达率随着FIGO分期(P=0.015和P=0.011)、淋巴结转移(P=0.001和P=0.001)及大网膜受累(P=0.028和P=0.018)显著降低。E-cadherin蛋白表达率随年龄增高显著降低(P=0.011),而p120蛋白表达率与年龄无显著相关性(P=0.226)。低级别浆液性癌中,仅p120蛋白表达率与淋巴结转移(P=0.042)、大网膜受累(P=0.048)及术前CA125水平(P=0.042)具有显著相关性。结论:卵巢高级别浆液性癌中p120蛋白的表达缺失率显著高于卵巢低级别浆液性癌,同时仅在高级别浆液性癌中E-cadherin和p120的低表达均与FIGO分期和肿瘤转移潜能相关,提示E-cadherin和p120蛋白可能在不同级别卵巢浆液性癌的发生发展中具有不同的作用。     

TRIF和MyD88指标在卵巢癌中的表达及与肿瘤血管生成的关系#br#

Objective?To explore the expression of TRIF and MyD88 markers in ovarian cancer and their relationship with tumor angiogenesis. Methods?The expressions of TRIF and MyD88 in 30 ovarian cancer tissues and normal ovarian tissues were detected; the relationship between TRIF and MyD88 and clinical case characteristics was analyzed; the correlation between TRIF and MyD88 and tumor angiogenesis was analyzed. Results?The positive expressions of TRIF, MyD88 and VEGF in ovarian cancer tissues were higher than those in normal ovarian tissues, and were correlated with FIGO staging and lymph node metastasis (P<0.05). The expression of TRIF, MyD88 and VEGF were positively correlated in ovarian cancer tissue, and mediate tumor angiogenesis. Conclusion?TRIF and MyD88 are highly expressed in ovarian cancer tissues, and together with VEGF mediate tumor angiogenesis, affecting the occurrence and development of ovarian cancer.     

Cathepsin D in ovarian cancer: prognostic value and correlation with p53 expression and microvessel density

OBJECTIVE: Overexpression of ubiquitous lysosomal aspartyl protease cathepsin D (CD) is involved in the progression of cancer. This study investigates the prognostic value and the association of cathepsin D expression with clinicopathological parameters, p53 expression, and angiogenesis in ovarian cancer. METHODS: Cathepsin D was determined immunohistochemically in 43 ovarian tumors of low malignant potential (LMP) and 80 invasive tumors FIGO stage I-IV. Results were correlated with clinicopathological characteristics, p53, and microvessel density (MVD). Survival analysis of cathepsin D expression and MVD was performed in invasive tumors. RESULTS: Epithelial tumor cathepsin D expression was more common in LMP tumors (65.1%) compared to invasive tumors (43.7%; P = 0.02). In LMP tumors, stromal cathepsin D was associated with mucinous tumors (P = 0.01), whereas in invasive tumors, epithelial cathepsin D expression was associated with clear cell tumors (P = 0.003). Invasive tumor cathepsin D had a negative relation to p53 expression. In LMP tumors, stromal cathepsin D correlated with microvessel density (P = 0.03). Stromal cathepsin D expression was an independent prognostic factor for disease-free survival (DFS) in patients with invasive cancer (P = 0.03, Cox regression), while cathepsin D expression missed to be of prognostic value for overall survival (OS) in invasive ovarian cancer. MVD had no influence on survival in invasive ovarian cancer (P > 0.05). CONCLUSION: Our study demonstrates a prognostic value of cathepsin D expression in invasive ovarian cancer, while cathepsin D expression in LMP tumors seems to be linked to angiogenesis. The relation among cathepsin D, p53 expression, and angiogenesis demonstrates biological differences between invasive ovarian cancer and LMP tumors.