转录因子 Sp1和 VEGF 在乳腺癌中的表达和意义

目的：检测转录因子 Sp1和 VEGF 在乳腺癌中的表达,探讨两者表达的相关性及临床意义。方法：采用免疫组织化学方法检测68例乳腺癌患者肿瘤组织及18例癌旁组织中 Sp1和 VEGF 的表达。结果：Sp1和 VEGF 在68例乳腺癌中表达的阳性率分别为72．05％（49／68）和64．71％（44／68）,与在18例正常乳腺组织中表达阳性率（分别为33．3％和16．67％）的差异有统计学意义（P 均＜0．01）。Sp1的过表达与乳腺癌的TNM分期、脉管浸润及淋巴结转移相关（P ＜0．05）,而与患者的年龄、肿瘤大小、组织学分级无明显相关性;在乳腺癌组织中 Sp1和 VEGF 的表达之间呈明显正相关（P ＜0．01）。结论：Sp1和 VEGF 的表达与乳腺癌的生物学行为密切相关,且 Sp1高表达与乳腺癌的血管生成及患者的预后相关。     

EB病毒潜伏膜蛋白LMP1、VEGF和cyclinD1在乳腺癌中的表达及其相关性

目的:探讨乳腺癌中EB病毒(Epstein-Barr virus,EBV)潜伏膜蛋白1(latent membrane protein 1,LMPl)、血管内皮生长因子(vascular endothelial growth factor,VEGF)和细胞周期蛋白D1(cyclinD1)的表达及其相关性.方法:收集乳腺癌标本构建组织芯片,应用免疫组化方法检测LMP1、VEGF和cyclinD1的表达,并结合临床病理因素进行相关分析.结果:乳腺癌组织中LMP1、VEGF及cyclinD1的表达率分别为17.8％(19/107)、85.0％ (91/107)和64.5％ (69/107);LMP1和cyclinD1的表达与患者年龄、肿瘤大小、病理学类型、淋巴结转移及脉管侵犯均无明显相关性(P＞0.05),而两者的表达均与组织学分级有关(P＜0.05);VEGF的表达与患者年龄、肿瘤大小、病理学类型、组织学类型及脉管侵犯均无明显相关(P＞0.05),而与淋巴结转移存在相关性(P＜0.05);LMP1的表达与VEGF和cyclinD1均明显相关(P＜0.05),同时,VEGF与cyclinD1表达明显相关(P＜0.05).结论:乳腺癌中LMP1可能直接上调VEGF的表达,或者LMP1通过促进cyclinD1的表达来上调VEGF的表达,从而对乳腺癌的淋巴转移及发生发展起到促进作用.     

乳腺癌组织中TGFβ1、VEGF、c-erbB-2的表达及其与浸润转移的关系

目的：探讨转化生长因子β1、血管内皮生长因子及c-erbB-2在乳腺癌组织中的表达及其与浸润转移的关系。方法：采用免疫组化EnVision^TM二步检测65例乳腺癌组织中TGFβ1，VEGF，c-erbB-2的表达情况。结果：TGFβ1，VEGF，c-erbB-2的表达均与乳腺癌淋巴结转移密切相关（P＜0．05或P＜0．01），TGFβ1表达还与癌浸润相关（P＜0．01），VEGF表达与TGFβ1,c-erbB-2表达呈显著正相关（P均＜0．01），结论：TGFβ1、VEGF和c-erbB-2的过度表达预示着乳腺癌具有较强的转移能力；3种蛋白的过度表达可能在乳腺癌的浸润转移过程中起协同作用。     

乳腺癌淋巴结转移与Ki67、VEGF表达的相关性及其临床意义

目的探讨乳腺癌淋巴结转移与VEGF（血管内皮生长因子）、K167表达的相关关系及其临床意义。方法采用免疫组化法检测125例乳腺癌组织中VEGF、Ki67的表达以及淋巴结转移的情况。结果腋窝淋巴结转移阳性率为72．8％．VEGF、Ki67表达阳性率分别为：56．8％和74．4％,VEGF与Ki67表达呈正相关（P〈0．01）,淋巴结转移与Ki67表达无显著相关（P〉0．05）,而与VEGF表达呈正相关（P〈0．01）：结论VEGF和Ki67在肿瘤的发生和发展过程中协同作用;Ki67及VEGF的表达与乳腺淋巴结转移是影响乳腺癌预后的重要因素。     

早期乳腺癌血清VEGF水平与骨髓微转移的相关性及临床意义

目的：检测早期乳腺癌患者血清中VEGF及骨髓标本中CK19的表达水平,探讨二者的相互关系及临床意义。方法：应用ELISA法分别检测6例乳腺纤维腺瘤及64例乳腺癌患者血清中VEGF的水平,同时抽取相应的骨髓血标本,应用实时定量逆转录-聚合酶链反应（qRT-PCR）方法检测标本中CK-19的表达水平,并进行相关性分析。结果：VEGF在乳腺癌患者血清中的表达水平明显高于乳腺纤维腺瘤患者,二者差异显著（P=0.012）;在HER2阳性患者中,血清VEGF水平明显高于HER2阴性患者（P=0.016）。CK19在乳腺纤维腺瘤患者骨髓标本中未见表达,在乳腺癌患者骨髓血中,阳性表达24例（37.5%）,而骨髓中CK19阳性的乳腺癌患者血清VEGF水平显著高于CK19阴性的患者（110.46±90.65 vs 70.88±77.13,P=0.038）,且二者的表达呈正相关。结论：早期乳腺癌患者血清VEGF水平与骨髓微转移密切相关,提示VEGF可能参与了肿瘤细胞的侵袭和播散,可作为早期乳腺癌微转移的血清学指标。     

早期乳腺癌血清VEGF水平与骨髓微转移的相关性及临床意义

目的 检测早期乳腺癌患者血清中VEGF及骨髓标本中CK19的表达水平,探讨二者的相互关系及临床意义.方法 应用ELISA法分别检测6例乳腺纤维腺瘤及64例乳腺癌患者血清中VEGF的水平,同时抽取相应的骨髓血标本,应用实时定量逆转录-聚合酶链反应(qRT-PCR)方法检测标本中CK-19的表达水平,并进行相关性分析.结果 VEGF在乳腺癌患者血清中的表达水平明显高于乳腺纤维腺瘤患者,二者差异显著(P=0.012);在HER2阳性患者中,血清VEGF水平明显高于HER2阴性患者(P=0.016).CK19在乳腺纤维腺瘤患者骨髓标本中未见表达,在乳腺癌患者骨髓血中,阳性表达24例(37.5%),而骨髓中CK19阳性的乳腺癌患者血清VEGF水平显著高于CK19阴性的患者(110.46±90.65 vs 70.88±77.13,P=0.038),且二者的表达呈正相关.结论 早期乳腺癌患者血清VEGF水平与骨髓微转移密切相关,提示VEGF可能参与了肿瘤细胞的侵袭和播散,可作为早期乳腺癌微转移的血清学指标.     

STIM1在宫颈癌中的表达及与VEGF的相关性

目的:探讨基质相互作用分子1(stromal interaction molecule 1,STIM1)在宫颈癌中的表达及其与VEGF的相关性.方法:收集20例宫颈癌患者的癌变及其正常上皮组织并测量对应肿瘤体积,采用免疫印迹法检测STIM1在各病变组织中的相对表达量,分析STIM1与肿瘤病变程度的相关性;酶联免疫ELISA方法测定过表达STIM1的癌细胞中血管内皮生长因子(VEGF)的分泌量并分析其与STIM1的相关性.结果:70%的宫颈癌组织中STIM1的表达上调,表达量与癌症病变标志物即肿瘤大小相关;STIM1可促进血管内皮因子VEGF的分泌.结论:STIM1在宫颈癌组织中高表达,是宫颈癌病变过程中的一个重要因子.     

VEGF在乳腺癌中的表达及其与ER、PR的相关性研究

目的：研究VEGF蛋白在乳腺癌中的表达情况及其与ER、PR的相关性。方法：采用免疫组织化学SP法检测VEGF、ER和PR在乳腺癌组织中的表达情况。结果：VEGF蛋白在乳腺癌和对照组乳腺良性病变组织中的阳性表达率分别为70.0%（42/60）和10.0%（2/20）,两者具有显著性差异（P〈0.01）。60例乳腺癌组织中ER表达37例呈阳性反应（37/60,61%）,PR表达36例呈阳性反应（36/60,60%）,VEGF蛋白在乳腺癌中的表达与ER标记指数呈负相关关系（P〈0.05）,和PR标记指数、发病年龄无关,与淋巴结转移、临床分期和病理分级密切相关。结论：VEGF蛋白在乳腺癌组织中表达上调,提示在乳腺癌的发生、发展中起重要作用,乳腺癌中VEGF、ER/PR联合检测,将对乳腺癌的治疗及预后判断起到互补作用,有一定临床应用价值。     

甲状腺癌组织中VEGF与TGF-β1的表达及其意义

目的探讨血管内皮生长因子（VEGF）及转化生长因子（TGF-β1）在甲状腺癌组织中的表达及其与临床病理特征的关系.方法对48例甲状腺乳头状腺癌,10例滤泡状腺癌组织标本,采用SP免疫组化染色法检测VEGF与TGF-β1的表达.结果 VEGF与TGF-β1在甲状腺癌组织中表达率分别为51.7%和56.9%,且随着肿瘤体积,病灶数量,病理分期的增加和淋巴结的转移而表达增多;两者在甲状腺癌中的表达阳性率呈正相关关系.结论 VEGF可促进肿瘤的增生和转移;在甲状腺癌的生长过程中,随着表达量由低到高,TGF-β1可能先起到抑制,而后促进肿瘤细胞生长的作用.     

Significance of vascular endothelial growth factor (VEGF)/soluble VEGF receptor-1 relationship in breast cancer

Angiogenesis, the formation of new blood vessels, is controlled by a balance between positive and negative endothelial regulatory factors. Soluble vascular endothelial growth factor receptor-1 (sVEGFR1), a naturally occurring soluble form of VEGFR1, is a negative counterpart of the vascular endothelial growth factor (VEGF) signaling pathway, which has been characterized as one of the most important endothelial regulators in human tumor angiogenesis. In our study, we examined the expression of sVEGFR1 in 110 primary breast carcinomas, and assessed its clinical significance. Ninety-four of 110 tumors showed > or = 0.1 ng/mg protein of sVEGFR1 (range:0. 1-6.9 ng/mg protein; median: 1.03 ng/mg protein) as determined by a specific enzyme-linked immunosorbent assay (ELISA). Immunoblot analysis confirmed the presence of sVEGFR1 in breast tumor tissues. The levels of sVEGFR1 were correlated significantly with the levels of VEGF. There was no significant correlation between the levels of sVEGFR1 and any clinico-pathological factors including age, menopause, nodal involvement and hormone receptor status. A univariate prognosis analysis showed that the intratumoral VEGF status, as determined by ELISA, was a significant prognostic indicator, but sVEGFR1 status was not. In the combined analysis, however, the ratio of sVEGFR1 and VEGF levels provided more statistically significant prognostic value than VEGF status alone. Tumors in which the sVEGFR1 levels exceeded VEGF levels 10-fold had a markedly favorable prognosis. Multivariate analysis also demonstrated that the ratio of sVEGFR1 and VEGF was an independent prognostic indicator after nodal status. In conclusion, sVEGFR1, an intrinsic inhibitor of VEGF, frequently co-expressed with VEGF in primary breast cancer tissues. The intratumoral balance between sVEGFR1 and VEGF levels might be crucial for the progression of breast cancer.     

Association between intratumoral free and total VEGF, soluble VEGFR-1, VEGFR-2 and prognosis in breast cancer

Vascular endothelial growth factor (VEGF) receptors consist of three cell-membrane type receptors (VEGFR-1, VEGFR-2 and VEGFR-3), and soluble form of VEGFR-1 (sVEGFR-1), an intrinsic negative counterpart of the VEGF. In this study, we measured intratumoral protein levels of free and total VEGF, VEGFR-2 and sVEGFR-1 from 202 primary breast cancer tissues and examined their prognostic values. A significant inverse correlation was found between free or total VEGF and oestrogen receptor (ER) status (P=0.042 and 0.032, respectively). A univariate analysis showed that low sVEGFR-1 and high total VEGF were significantly associated with poor prognosis in disease-free survival (DFS) and overall survival (OS). The ratio of sVEGFR-1 to total VEGF was a strong prognostic indicator (DFS: P=0.008; OS: P=0.0002). A multivariate analysis confirmed the independent prognostic values of total VEGF and the ratio of sVEGFR-1 to total VEGF. In subgroup analysis, total VEGF was a significant prognostic indicator for ER-positive tumours but not for ER-negative tumours, whereas sVEGFR-1 was significant for ER-negative tumours but not for ER-positive tumours. In conclusion, the intratumoral sVEGFR-1 level, VEGF level and the ratio of sVEGFR-1 to total VEGF are potent prognostic indicators of primary breast cancer, and might be relevant to ER status.     

The prognosis was poorer in colorectal cancers that expressed both VEGF and PROK1(No correlation coefficient between VEGF and PROK1)

The angiogenic proteins vascular endothelial growth factor (VEGF) and prokineticin1 (PROK1) proteins are considered important in colorectal cancer, the relationship between their simultaneous expression and prognosis was investigated in the present study.VEGF and PROK1 expression in 620 primary human colorectal cancer lesions was confirmed via immunohistochemical staining with anti-VEGF and anti-PROK1 antibodies, and the correlation between the expression of these 2 proteins and recurrence/prognosis were investigated.VEGF protein was expressed in 329 (53.1%) and PROK1 protein was expressed in 223 (36.0%). PROK1 and VEGF were simultaneously expressed in 116 (18.7%) of the 620 cases. The correlation coefficient between VEGF expression and PROK1 expression was r = 0.11, and therefore correlation was not observed. Clinical pathology revealed that substantially lymphnode matastasis, hematogenous metastasis, or TMN advanced-stageIV was significantly more prevalent in cases that expressed both VEGF and PROK1 than in the cases negative for both proteins or those positive for only 1 of the proteins.Also the cases positive for both proteins exhibited the worst recurrence and prognosis. In the Cox proportional hazards model, VEGF and PROK1 expression was an independent prognostic factor.The prognosis was poorer in colorectal cancers that expressed both PROK1 and VEGF relative to the cases that expressed only 1 protein, and the expression of both proteins was found to be an independent prognostic factor.     

HER-2阴性乳腺癌中VEGF、COX-2的表达及相关性研究

目的:研究血管内皮生长因子（VEGF）、环氧化酶-2（COX-2）在91例HER-2阴性乳腺癌组织中的表达及相互关系,分析其与临床病理特征及预后的关系。方法:采用免疫组化SABC法,检测91例HER-2阴性乳腺癌组织中VEGF、COX-2蛋白的表达,并与临床病理特征进行相关性分析。结果:HER-2阴性乳腺癌组织中VEGF阳性表达率为94.5%,其中47.2%为高表达（+++）,VEGF的表达与肿瘤大小、淋巴结转移相关（P<0.05）。HER-2阴性乳腺癌组织中COX-2阳性表达率为86.8%,其中34.0%为高表达（+++）,COX-2的表达与患者年龄、组织学分级、肿瘤大小、淋巴结转移及TNM分期无关（P>0.05）。VEGF与COX-2的表达呈正相关（r=0.1798,P=0.018）,VEGF/COX-2均高表达的患者淋巴结转移率高。结论:VEGF、COX-2在HER-2阴性乳腺癌组织中均高表达且两者呈正相关,联合检测VEGF、COX-2的表达对HER-2阴性乳腺癌预后判断可能具有重要价值。     

VEGF、COX-2、MMP-9在乳腺癌组织中的表达对乳腺钼靶x线征象的影响

目的探讨乳腺癌组织中血管内皮细胞生长因子（VEGF）、环氧化酶-2（COX-2）、基质金属蛋白酶-9（MMP-9）的表达对乳腺钼靶x线征象的影响,并初步探讨乳腺钼靶x线征象与分子病理学之间的关系。方法收集经乳腺钼靶X线检查、手术和病理证实的乳腺癌患者69例,将乳腺钼靶x线征象分为毛刺征、钙化征、异常血管征、淋巴结转移征,分析VEGF、COX-2、MMP-9表达对以上征象的影响。结果乳腺钼靶x线征象有毛刺征组VEGF、COX-2、MMP-9阳性表达率明显高于无毛刺征组（P〈0．05）;钙化组与无钙化组VEGF、COX-2、MMP-9阳性表达率差异无统计学意义（P〉0．05）;有异常血管征组VEGF、COX-2、MMP-9阳性表达率明显高于无异常血管征组（P〈0．05）;有淋巴结转移征组VEGF、COX-2、MMP-9阳性表达率明显高于无淋巴结转移征组（P〈0．05）。结论VEGF、COX-2、MMP-9高表达对乳腺钼钯x线征象毛刺征、异常血管征、淋巴结转移征的出现存在影响,并可作为乳腺钼钯X线恶性征象的生物学基础。     

环氧合酶-2和血管内皮生长因子-C在乳腺癌组织中的表达及预后生存分析

[目的]评价乳腺癌组织中环氧合酶-2(COX-2)和血管内皮生长因子-C(VEGF-C)在基因及蛋白水平表达,分析两者与乳腺癌患者预后的关系.[方法]采用免疫组化SP法和QRT-PCR法分别检测150例乳腺癌组织中COX-2和VEGF-C在mRNA和蛋白水平表达,并采用Kaplan-meier法和COX风险回归模型分析与乳腺癌预后生存的相关危险因素.[结果]乳腺癌组织中COX-2和VEGF-C在mRNA和蛋白水平率均高于乳腺良性组织(58.8％ vs 41.2％和58.9％ vs 41.1％,P＜0.01).单因素结果显示患者COX-2表达、临床分期、腋窝淋巴结转移、Her-2表达、组织学分级与患者的预后有关;COX多因素分析显示肿瘤大小和腋窝淋巴结是影响乳腺癌患者预后的因素.[结论]乳腺癌患者COX-2和VEGF-C表达上调,乳腺癌组织中肿瘤大小、腋窝淋巴结转移是乳腺癌患者预后的影响因素.     

3种肿瘤相关蛋白与直肠癌浸润和转移的关系

[目的]检测直肠癌组织中与浸润转移过程相关的蛋白钙粘素(E—cad)、基质金属蛋白酶—9（MMP—9)、血管内皮细胞生长因子(VEGF)的表达，探讨这些因素与大肠癌浸润、转移的相关性，以期寻找能够进一步判断大肠癌浸润转移潜能的分子生物学指标。[方法]采用免疫组化SP方法检测90例直肠癌中E-cad、MMP-9、VEGF的表达。[结果]E-cad的表达随着癌组织的分化程度的降低而降低，随浸润深度的加深及转移的出现逐渐下调。MMP-9的表达随着浸润深度的加深及淋巴结转移的出现而逐渐增强。VEGF的表达与淋巴结转移呈正相关。[结论]直肠癌的浸润和转称与E-cad、MMP-9、VEGF的表达具有显著相关性。应用多种抗体检测肿瘤相关蛋白并分析其表达的意义，将有助于判断直肠癌的浸润、转移潜能及预后，为临床治疗方案的选择提供理论依据。