膀胱移行细胞癌血管内皮生长因子的表达及临床意义

目的探讨血管内皮生长因子与膀胱癌浸润及复发的关系。方法应用ＬＳＡＢ免疫组织化学技术检测４０例膀胱移行细胞癌血管内皮生长因子（ＶＥＧＦ）的表达。结果膀胱癌细胞ＶＥＧＦ的表达率为５５％（２２／４０）,浸润性癌组ＶＥＧＦ的表达显著高于表浅性癌组（Ｐ＜０．０１）,有淋巴结转移癌组显著高于无转移癌组（Ｐ＜０．０５）,复发性癌组较初发性癌组差异有显著性（Ｐ＜０．００１）。结论ＶＥＧＦ可作为判断膀胱癌生物学行为的指标之一。     

膀胱移行细胞癌VEGF表达和MVD检测的临床意义

目的　探讨膀胱移行细胞癌组织中血管内皮细胞生长因子（ＶＥＧＦ） 的表达与肿瘤间质微血管密度（ＭＶＤ）检测的临床意义。　方法　采用免疫组化方法对７７ 例膀胱移行细胞癌及１０ 例正常膀胱组织进行ＶＥＧＦ多克隆抗体及第Ⅷ因子相关抗原（ＶＷＦ：Ａｇ） 单克隆抗体染色,观察膀胱移行细胞癌ＶＥＧＦ的表达与ＭＶＤ 之间的相关性。　结果　ＶＥＧＦ的表达与肿瘤间质微血管密度之间存在正相关性,二者均与膀胱移行细胞癌的病理分级显著相关,浸润性肿瘤明显高于浅表性肿瘤（Ｐ＜０ ．０５） ;术后随访６ 年,术后２ 年内复发组明显高于６ 年内未复发组（ Ｐ＜ ０ ．０５） ,但与肿瘤大小、性别、年龄无关。　结论　ＶＥＧＦ的表达为膀胱移行细胞癌的恶性表型,并与膀胱肿瘤间质微血管形成有关,上述二项指标对评估膀胱移行细胞癌的预后有重要意义。     

膀胱移行细胞癌微血管密度与肿瘤复发的关系

目的：探讨肿瘤微血管形成能力与膀胱移行细胞癌复发的关系及其机制,方法：采用免疫组织化学方法对２５例膀胱移行细胞癌组织中ＶＩＩＩ因子相关抗原、碱性成纤维细胞生长因子（bFGF)及血管内皮细胞生长因子（ＶＥＧＦ）分别进行特异性染色,计数肿瘤内微血管密度（iWV),并观察bＦＧＦ、ＶＥＧＦ的表达,结果：ＶＥＧＦ和bFGＦ的阳性表达率分别为４８％和２８％,阳性表达组iMV显才高于阴性表达组（Ｐ＜０．０５）,术后复发组iMV显著高于未复发组（Ｐ＜０．０５）,且高iMV组复发率高于低iMV组（Ｐ＜０．０５）,结论：iMV与膀胱移行细胞癌复发有关,而促血管形成因子的异常表达是其微血管形成能力增高的重要因素。     

膀胱癌组织中血管内皮生长因子的表达及与血管生成的关系

目的 探讨血管内皮生长因子（ＶＥＧＦ）在原发性膀胱移行细胞癌中的表达及其与膀胱癌血管生成之间的关系。方法 免疫组织化学技术检测６８例原发性膀胱移行细胞癌和７例正常膀胱组织中血管内皮生长因子的表达,测定４０例浸润性膀胱癌的微血管密度,并分析ＶＥＧＦ和ＭＶＤ间以及它们与膀胱癌病理分级和临床分期间的关系。结果 ＶＥＧＦ在正常膀胱中不表达或低表达,而在膀胱表达较强;ＶＥＧＦ表达及ＭＶＤ值均与肿瘤的病理分级     

膀胱移行细胞癌肿瘤血管生成的研究

为探讨肿瘤微血管与膀胱移行细胞癌浸润和转移的关系，应用免疫组织化学技术在６４例膀胱移行细胞癌组织中对第Ⅷ因子相关抗原进行表达，并计数肿瘤的微血管（ＭＶ）。结果发现，术后复发者ＭＶ数明显高于未复发者（Ｐ＜００１），浸润性癌的ＭＶ数明显高于浅表性癌（Ｐ＜００１），组织学Ⅲ级高于Ⅰ、Ⅱ级（Ｐ＜００５），伴淋巴结转移的ＭＶ数显著高于未转移者（Ｐ＜００５）。结果提示以ＭＶ为标记的肿瘤血管与膀胱移行细胞癌的分期、分级及预后密切相关，肿瘤的增长和转移有赖于肿瘤血管的生成。     

血管内皮生长因子在肾细胞癌中的表达及意义

研究肾细胞癌血管内皮生长因子（ＶＥＧＦ）的表达及其与肿瘤转移、分期、病理类型及预后的关系。采用抗ＶＥＧＦ的多克隆抗体免疫组织化学技术染色（ＬｓＡＢ法）研究６１例肾癌组织切片。结果显示：４５９％（２８／６１）的肾癌ＶＥＧＦ表达阳性，淋巴结和（或）血行转移的ＶＥＧＦ表达率（７７８％）明显高于非转移者（３２６％，Ｐ＜００１）；阳性表达者五年生存率（２９１％）明显低于阴性表达者（８４６％，Ｐ＜００１）；Ⅰ、Ⅱ期阳性表达低于Ⅲ、Ⅳ期（Ｐ＜００５）；但与性别、年龄及肿瘤的病理类型无关。ＶＥＧＦ除在癌细胞胞浆和胞膜表达外，尚表达于肿瘤基质血管和邻近肿瘤的正常肾小管胞浆、肾小球和血管内皮及血管平滑肌胞膜。认为ＶＥＧＦ除由肿瘤细胞合成外，可能尚表达于邻近肿瘤的正常肾小管胞浆，ＶＥＧＦ表达有助于肾癌预后判断及指导治疗，ＶＥＧＦ可能是肿瘤血管的良好标记物，设法抑制ＶＥＧＦ可望成为肾癌治疗的有效方法。     

膀胱癌组织血小板衍生生长因子受体表达研究

为研究血小板衍生生长因子受体（ＰＤＧＦＲ）表达与膀胱移行上皮细胞癌的关系，采用免疫组织化学ＳＰ法观察４３例膀胱癌、１１例正常膀胱、１４例癌旁正常膀胱组织ＰＤＧＦＲ表达。结果发现ＰＤＧＦＲ阳性染色分布于癌细胞、间质、血管及炎症细胞的胞浆、胞膜及核膜。膀胱部组织ＰＤＧＦＲ阳性率为８１．４％，明显高于正常及癌旁膀胱组织，统计学上有极显著性差异（Ｐ〈０．０１）。研究表明ＰＤＧＦＲ表达与正常组织生长有关，过     

膀胱移行细胞癌血和内皮生长因子的表达及临床意义

目的 探讨血管内皮生长因子与膀胱癌浸润及复发的关系。方法 应用ＩＳＡＢ免疫组织化学技术检测４０例光移行细胞癌血管内皮生长因子（ＶＥＧＦ）的表达。结果 膀胱癌细胞ＶＥＧＦ的表达率为５５％,浸润性癌组ＶＥＧＦ的表达显著高于表浅性癌组,有淋巴结转移癌组显著高于无转移癌组,复发且较初发性癌组差异有显著性。结论ＶＥＧＦ可作为判断膀胱癌生物学行为的指标之一。     

TGF－β_1蛋白的表达对膀胱癌生物学行为的影响

应用ＴＧＦ－β_１放免分析方法对１８例膀胱移行细胞癌进行研究，并选取９例正常膀胱为对照。结果显示：膀胱癌组织中ＴＧＦ－β_１蛋白表达量显著高于正常膀胱粘膜（Ｐ＜０．００１）。分期Ｔ_１组和Ｔ_２组ＴＧＦ－β_１蛋白表达量显著高于Ｔａ组（Ｐ＜０．０５和Ｐ≤０．００５）。Ｇ３组ＴＧＦ－β_１蛋白表达量显著高于Ｇ_１组（Ｐ≤０．０５）。应用￣３Ｈ－ＴｄＲ掺入实验研究表明：ＴＧＦ－β_１在体外可促进ＴＢＣ－１系膀胱癌细胞的体外生长。本组结果提示：ＴＧＦ－β_１蛋白的表达对膀胱癌的生物学行为有重要影响，对评估膀胱癌预后有重要意义。     

膀胱移行细胞癌微血管分型及意义

为探讨膀胱移行细胞癌组织中肿瘤微血管不同类型与浸润和转移的关系，应用免疫组织化学ＳＰ法在６１例膀胱移行细胞癌组织中对第Ⅷ因子相关抗原进行表达并计数，根据肿瘤组织中微血管（ＭＶ）的分布特点及其与肿瘤组织的关系，将ＭＶ分为两型：Ⅰ型为肿瘤组织内ＭＶ，位于癌组织内，血管迂曲，扩张，变形；Ⅱ型为肿瘤旁ＭＶ，位于肿瘤边缘，血管分布不均。结果显示浸润性癌组的Ⅱ型ＭＶ数显著高于Ⅰ型ＭＶ数（Ｐ＜００５），在浅表性癌组中Ⅰ，Ⅱ型ＭＶ数之间无显著性差异（Ｐ＞００５），伴淋巴结转移的癌组织Ⅱ型ＭＶ数显著高于Ⅰ型ＭＶ数（Ｐ＜００５）。认为肿瘤血管的生长有很大的异质性，肿瘤边缘的微血管与肿瘤的浸润有密切关系。     

膀胱移行细胞癌中环氧化酶-2表达及其预后价值

目的探讨与膀胱移行细胞癌预后相关的新诊断方法。方法采用免疫组化SP法,检侧68例原发性膀胱移行细胞癌和10例正常膀胱组织标本环氧化酶-2(COX-2)的表达,结合临床资料,探讨其相互联系以及其表达与预后的关系。结果68例膀胱移行细胞癌组织中COX-2阳性表达率为63.2%(43/68),与病理分级、临床分期、血管浸润有关(P<0.05),而与淋巴结是否转移无显著性差异(P>0.05);对照组10例正常膀胱黏膜COX-2表达均为阴性;COX-2表达阳性生存超过5年者(54.1%)明显低于COX-2表达阴性者(91.3%)(P<0.05)。结论COX-2表达与膀胱移行细胞癌的恶性程度密切相关,检测COX-2表达对判断膀胱移行细胞癌预后有重要意义。     

Clinical relevance of maspin expression in bladder cancer

Transitional cell carcinoma (TCC) of the bladder is a solid tumor that induces angiogenesis to maintain nutrition and oxygenation of tumor cells. Maspin, a serpin with tumor suppressing activity, has recently been identified as an inhibitor of angiogenesis. This study examined the impact of maspin expression in the growth pattern of TCC of the bladder. Maspin was identified in a panel of normal tissues, in several bladder carcinoma cell lines, and 51 patient samples of TCC of the bladder. Expression was detected by RT-PCR and immunohistochemistry. Furthermore, the level of maspin was correlated to the growth rate of bladder tumor cell lines in vitro and in vivo. Maspin expression was found in high quantities in normal urothelium. Maspin expression was preserved in superficial bladder cancers but was significantly diminished in invasive carcinomas. Within the group of invasive TCCs, maspin expression was inversely correlated to the patient prognosis. Furthermore, low maspin expression level was coupled to an increased tumor cell growth in vivo. Down-regulation of maspin expression seems to be a specific event in the progression of invasive bladder carcinoma. Maspin might be a useful marker to determine the prognosis of invasive TCC. Furthermore, maspin re-expression might become a therapeutic option in the treatment of invasive, metastatic TCC.This study was supported in part by Medac GmbH.     

The expression of vascular endothelial growth factor in transitional cell carcinoma of urinary bladder is correlated with cancer progression

Vascular epithelial growth factor (VEGF) regulates neovascualrization in malignant cells. VEGF as a mitogen is thought to alter cancer cell formation and tumor progression. We aimed to investigative the expression of the VEGF gene to evaluate their clinical significance in transitional cell carcinoma (TCC) of urinary bladder. Tissue samples from 161 patients with TCC were examined with an immunohistochemical stain for the expression of the VEGF gene. The expression rate was compared to 32 normal bladder mucosal samples obtained from transurehtral surgery from noncancer patients. The results revealed significant differences between normal urothelium (0%) and cancer tissue (54.7%) for the positive staining of VEGF protein (P < 0.001). With the progression of tumor grade and clinical staging, the positive rate of VEGF gene expression significantly increased. Expression of the VEGF gene in the invasive group was greater than that in the noninvasive group (P < 0.001). The results revealed that expression of the VEGF gene is proportional to the formation and progression of TCC. Therefore, abnormal expression of VEGF genes can be used as a prognostic marker in TCC of urinary bladder.     

EZH2基因在膀胱移行细胞癌细胞株和癌组织标本中的表达及意义

目的 探讨EZH2基因在膀胱癌发生及进展中的作用. 方法 应用RT-PCR、蛋白质印迹及免疫细胞化学方法,以前列腺癌细胞株PC-3M作为阳性对照,检测EZH2基因在人膀胱移行细胞癌细胞株T24、EJ、MGH-U1、BIU-87中的表达;采用RT-PCR方法检测45例膀胱移行细胞癌和12例正常膀胱黏膜组织中EZH2基因表达情况.45例膀胱移行细胞癌中表浅性癌(Tis、Ta、T1)31例(68.9%),浸润性癌(T2～T4)14例(31.1%);病理分级G1 13例(28.9%),G2 21例(46.7%),G3 11例(24.4%). 结果 4种膀胱癌细胞株中均有EZH2基因表达.EZH2基因在膀胱移行细胞癌组织中的表达率(82.2%)明显高于正常膀胱黏膜(8.3%,P<0.05),在表浅性膀胱癌中的表达率为74.2%,浸润性膀胱癌中为100.0%,差异无统计学意义(P>0.05).EZH2基因在G1,G2和G3级肿瘤中的表达率分别为61.5%,85.7%和100.0%.随细胞分级程度升高.EZH2表达率有增加趋势,但差异无统计学意义(P>0.05). 结论 EZH2基因可能在膀胱癌的发生及进展中起重要作用,可能成为膀胱癌一个潜在的基因治疗靶点.     

基质金属蛋白酶-9和血管内皮生长因子在膀胱移行上皮细胞癌中的表达及其临床意义

目的探讨基质金属蛋白酶-9（MMP-9）和血管内皮生长因子（VEGF）在膀胱移行上皮细胞癌（BTCC）中的表达及其临床意义。方法采用免疫组织化学SP法检测46例BTCC和10例正常膀胱黏膜组织中MMP-9和VEGF的表达。结果MMP-9和VEGF的阳性表达率在BTCC组中分别为76．09％和67．39％,均显著高于正常组,两组比较差异有统计学意义（P〈0．01）;BTCC中两种蛋白表达水平在高分化组与中低分化组之间、Tis-T1期与T2-T4期间的差异均有统计学意义（P〈0．05）。MMP-9和VEGF两者表达呈正相关。结论MMP-9和VEGF与膀胱移行上皮细胞癌的恶性程度有关,并可作为研究膀胱肿瘤的生物学行为和判断预后的参考指标。     

Differential C-erbB-2 and VEGF expression following BCG immunotherapy in superficial papillary transitional cell carcinoma of the bladder

Bacillus Calmette Guerin (BCG) is generally regarded as an effective immunotherapy for superficially invasive papillary transitional cell carcinoma of the bladder. The exact mechanism(s) which underlie its efficacy are unknown. As C-erbB-2 oncoprotein and vascular endothelial growth factor (VEGF) have been shown to be over-expressed in TCC of the bladder, it has been postulated that they may be important in its pathogenesis. The purpose of this study was to 1.) differentially evaluate the effect of BCG immunotherapy in treated and untreated cohorts on the immunohistochemical expression of C-erbB-2 and VEGF in formalin-fixed paraffin-embedded sections of superficial and superficially invasive (Stage Ta-T1) transitional cell carcinoma of the bladder. Immunolabeling intensity was assessed independently by two pathologists and reported as a mean labeling index. The results confirm previous studies that 1.) both c-erbB-2 and VEGF are over-expressed in these tumors MLI = 90.1 and 45.7 respectively, 2.) that VEGF is an early and sensitive indicator of TCC, and 3.) that BCG has a salutary effect on papillary TCC, 66% vs. 89% recurrence rate, P = .04. Our findings show that 1.) C-erbB-2 expression is decreased in patients tumors which show response to BCG (45.7 to 38.5), P = 0.15, 2.) that BCG administration has no effect on the expression of VEGF. While the decrement in c-erbB-2 immunostaining observed in those patients who received BCG contrasts with the increase in c-erbB-2 immunolabeling observed in patients who did not receive BCG, the differences were not statistically significant and could reflect tumor grade or stage regression associated with BCG therapy. However, this study suggests that BCG differentially influences the expression of C-erbB-2 and VEGF.