p53,CD34,E-钙粘蛋白在膀胱癌中的表达及判断预后的价值

目的　探讨 p5 3、CD3 4 、E 钙粘蛋白 (E cadherin)在膀胱移行细胞癌中的表达及判断膀胱癌预后的价值。　方法　采用免疫组化方法检测 4 6例膀胱移行细胞癌和 8例正常膀胱粘膜标本p5 3、CD3 4 、E cadherin的表达情况。　结果　 4 6例膀胱癌标本中p5 3、E cadherin的异常表达率分别为2 1.7%和 4 5 .6 %。p5 3异常表达在表浅型膀胱癌为 9.1% ,浸润型为 33.3% ,差别有显著性意义 (P <0 .0 5 ) ;病理Ⅰ～Ⅱ级异常表达 7.1% ,Ⅲ级 4 4 .4 % ,差别有显著性意义 (P <0 .0 0 5 ) ;复发组异常表达89 % ,未复发组 15 % ,差别有显著性意义 (P <0 .0 0 5 )。E Cadherin的异常表达率在浅表型膀胱癌为77.3% ,浸润型为 33.3% ,差别有显著性意义 (P <0 .0 0 5 ) ;在Ⅰ、Ⅱ级膀胱癌为 71.4 % ,Ⅲ级为2 7.8% ,差别有显著性意义 (P <0 .0 0 5 ) ;在复发组与未复发组分别为 18.0 %和 6 1.0 % ,差别有显著性意义 (P <0 .0 1)。CD3 4 在膀胱癌中的异常表达率为 4 1.3% ,在不同分期分级及复发与未复发组之间的表达差别均无显著性意义。　结论　p5 3和E Cadherin的异常表达与膀胱癌的恶性程度及复发密切相关 ,可作为判定肿瘤预后和复发的分子生物学指标     

E-钙粘素和β-连环素在膀胱移行细胞癌的表达及其意义

目的 :探讨E 钙粘素 (E cad)和 β 连环素 (β cat)的表达与膀胱移行细胞癌病理分级、临床分期以及预后的关系。方法 :应用免疫组织化学方法检测 5 8例膀胱移行细胞癌中E cad和 β cat的表达。 结果 :5 8例中E cad和 β cat的异常表达率分别为5 0 .0 %和 5 3.5 % ,二者同时正常或异常表达者为 79.3% ,二者表达之间具有显著相关性 (P <0 .0 1) ,并且二者中至少有一个异常表达者为 6 5 .5 %。E cad和 β cat在Ⅰ、Ⅱ、Ⅲ级肿瘤中的异常表达率分别为 11.1%、5 2 .9%、78.3%和 2 7.7%、4 1.2 %、82 .6 % ,上述的异常表达率在病理分级间比较差异均有极显著性意义 (P <0 .0 1)。E cad和 β cat在浅表组、浸润组的异常表达率分别为2 0 .8%、70 .6 %和 33.3%、76 .5 % ,两组比较差异均有极显著性意义 (P <0 .0 1)。E cad和 β cat正常表达组与异常表达组之间 2年生存率差异分别有极显著性或显著性意义 (P <0 .0 1,P <0 .0 5 )。结论 :E cad和 β cat异常表达与膀胱移行细胞癌的恶性程度有关 ,可以作为检测膀胱移行细胞癌分期、分级及预后的重要指标     

膀胱移行细胞癌Id-1表达的实验研究

目的　探讨正常膀胱移行上皮和不同分化程度膀胱移行细胞癌 (BTCC)Id 1的表达 ,分析膀胱癌生物学行为与Id 1的关系。方法　免疫组化ABC法检测 111例BTCC和 12例正常膀胱组织Id 1表达。结果　Id 1正常膀胱组织 3例表达阳性 ,阳性率 2 5 % ;BTCC 97例表达阳性 ,阳性率 87.38% ,膀胱癌G1、G2 、G3 阳性率分别为 88.89%、87.5 %、85 .72 % ,与对照组比较均有显著性差异 (P <0 .0 1) ,病理分级间无显著性差异 (P >0 .0 5 ) ;表浅性膀胱癌与浸润性膀胱癌表达阳性率分别为 82 .76 %、92 .4 5 % ,两者比较具有统计学意义 (P <0 .0 5 )。结论　膀胱移行细胞癌Id 1过表达 ;Id 1与膀胱癌发生和侵袭性有一定关系 ;Id 1可能作为膀胱癌的一种肿瘤标记物为膀胱癌的筛查、早期诊断和术后随访提供帮助。     

表浅性膀胱移行细胞癌中p53和Bcl-2同时表达的临床意义

目的 :探讨表浅性膀胱移行细胞癌中Bcl 2和 p5 3的同时表达与膀胱癌预后之间的关系。 方法 :应用免疫组化技术 (SABC法 )检测 4 2例表浅性膀胱癌蜡块标本中Bcl 2和p5 3的表达。患者术后平均随访 36个月 ,14例复发 ,其中复发 2次以上 9例 ,有转移者 4例。结果 :4 2例中 ,31例 (73.8% ) p5 3阳性表达 ,与G1(6 2 .5 % )和G2 (72 .2 % )相比较 ,G3 (81.2 % )更多见 ;pT1期 (78.6 % )p5 3阳性率较 pTa期 (6 4 .3% )高。 12例(2 8.6 % )发现有Bcl 2表达 ,Bcl 2表达阳性率G3 (37.5 % )明显高于G2 (2 2 .2 % )和G1(2 5 .0 % ) ,与分期无关 (P>0 .0 5 )。膀胱癌复发率p5 3基因表达阳性者高于阴性者 (P <0 .0 5 ) ,而Bcl 2基因表达阳性者与阴性者的差别无统计学意义 (P >0 .0 5 ) ,但 p5 3和Bcl 2同时呈阳性表达者 (8例 )明显高于其他患者 (P <0 .0 1)。Bcl 2和p5 3的阳性表达与肿瘤侵袭性和淋巴结及远处转移有关。结论 :p5 3和Bcl 2同时阳性表达的肿瘤患者预后较差 ,两者同时检测对判断膀胱癌复发及预后更具有指导意义。     

膀胱癌患者尿脱落细胞中细胞角蛋白20的表达及临床意义

目的　探讨膀胱癌患者尿脱落细胞中细胞角蛋白 2 0 (CK2 0 )的表达及临床意义。　方法　采用RT PCR方法检测 4 1例膀胱癌、2 0例其他泌尿系疾病患者及 10例正常人尿脱落细胞中CK2 0的表达。　结果　 10例正常人的尿脱落细胞均未表达CK2 0 ;2 0例非膀胱癌者中 3例表达CK2 0 ;4 1例膀胱癌患者中 37例表达CK2 0 ,三组间比较差别有显著性意义 (P <0 .0 1)。G1、G2 及G3膀胱癌的阳性率分别为 90 .2 % (2 3/2 5 )、88.8% (8/9)及 85 .7% (6 /7) ,三组比较差别无显著性意义(P >0 .0 5 )。　结论　CK2 0在膀胱癌患者尿脱落细胞中表达阳性率高 ,可用于膀胱癌的诊断及术后随访。     

上皮钙粘蛋白/连接素复合体在膀胱癌中表达及对预后的判断价值

目的 :探讨上皮钙粘蛋白 /连接素 (E cd/cat)复合体在膀胱癌中的表达及对判断膀胱癌的复发及预后的价值。方法 :应用免疫组织化学法 (SP法 )检测 72例膀胱移行细胞癌和 10例正常泌尿系移行上皮石蜡包埋标本中E cd/cat复合体的表达情况。结果 :10例正常泌尿系移行上皮E cd/cat复合体各组成成分均正常表达。膀胱移行细胞癌中E cd、α cat、β cat、γ cat异常表达率分别为5 6 .9% (4 1/ 72 )、4 4 .4 % (32 / 72 )、5 6 .9% (4 1/ 72 )、4 3.1% (31/ 72 )。E cd和cat表达具有显著相关性 (P<0 .0 1)。E cd/cat复合体异常表达率与膀胱癌的病理分级和临床分期密切相关 (P <0 .0 5 )。β cat的异常表达与所有肿瘤的复发相关 (P <0 .0 5 )。α cat异常表达与表浅肿瘤 (Tis～T1期 )的复发密切相关 (P <0 .0 1)。γ cat异常表达与肿瘤的生存预后密切相关 (P <0 .0 1)。结论 :E cd/cat复合体的异常表达与膀胱癌的分化和侵袭程度密切相关。β cat是膀胱肿瘤复发预后的较好指标。α cat是表浅肿瘤复发预后的较好指标。γ cat是膀胱癌生存预后的有价值指标。     

膀胱癌组织及血清中内皮抑素表达的意义

目的　探讨原发性膀胱癌患者血清内皮抑素水平和组织表达与肿瘤分级、分期的关系。　方法　采用免疫组织化学方法检测 4 5例膀胱癌组织及 12例正常膀胱组织中内皮抑素表达情况。ELISA法检测 5 8例膀胱癌患者术前血清内皮抑素水平 ,4 3例健康者血清作对照。　结果　浅表性膀胱癌组内皮抑素表达率 6 1.5 % ,浸润性癌组为 90 .6 % ,正常膀胱组织为 33.3%。膀胱癌患者血清内皮抑素 4 6 .3ng/ml,显著高于对照组的 2 9.8ng/ml(P <0 .0 1)。局部浸润性膀胱癌患者血清内皮抑素 4 8.6ng/ml,显著高于浅表性癌组的 31.1ng/ml(P <0 .0 1) ;远处转移组血清内皮抑素 6 9.8ng/ml,显著高于局部浸润组 (P <0 .0 1) ;浅表性癌组与对照组血清内皮抑素水平差异无显著性意义。G3级肿瘤患者血清内皮抑素水平显著高于G1和G2 级 (P <0 .0 1)。　结论　膀胱癌患者血清内皮抑素水平和组织表达显著增高 ,并与肿瘤分级、分期相关 ,检测内皮抑素表达及血清水平有助于判断膀胱癌的恶性程度。     

T1G3膀胱癌术后卡介苗维持膀胱灌注能降低复发率吗?

目的 探讨卡介苗(BCG)维持膀胱灌注对T1G3浅表性膀胱癌术后复发的影响. 方法应用Meta分析固定效应模型和随机效应模式对有关BCG维持灌注与T1G3浅表性膀胱癌术后复发的文献进行综合定量评价,并进一步采用分层分析判定不同BCG菌株与T1G3浅表性膀胱癌术后复发的具体关系. 结果纳入Meta分析15篇文献1648例患者,其中采用BCG灌注治疗915例,未采用BCG灌注治疗733例.术后腔内维持灌注BCG者膀胱癌复发率为41.0%(375/915),未灌注组为45.3%(332/733).BCG维持灌注与T1G3浅表性膀胱癌术后复发的合并OR值为0.58(95%可信区间0.41～0.83,P=0.003),不同BCG菌株维持灌注与T1G3浅表性膀胱癌术后复发的合并OR值分别为0.50(95%可信区间0.26～0.95,P=0.04)和0.63(95%可信区间0.40～0.99,P=0.04).结论 BCG维持灌注可有效降低T1G3浅表性膀胱癌患者术后的复发率.     

Smad4在膀胱癌发生中的作用

目的　探讨Smad4 在膀胱癌发生中的作用。　方法　采用免疫组化方法对 4羟丁基亚基硝胺 (BBN)诱导大鼠膀胱癌组织Smad4 表达进行观察分析。　结果　Smad4 在增生膀胱粘膜中阳性表达率为 2 4% (5 / 2 1) ,膀胱癌组织中为 5 3% (17/ 32 ) ,P <0 .0 5。G1阳性表达率 35 % (7/ 2 0 ) ,G2 83 %(10 / 12 ) ,P <0 .0 5。Ta阳性表达率 36 % (8/ 2 2 ) ,T190 % (9/ 10 ) ,P <0 .0 5 ,差别均有显著性意义。随BBN作用时间延长膀胱癌组织Smad4 阳性表达率升高。　结论　Smad4 与大鼠膀胱癌形成有关 ,随病理分期、细胞分级增高阳性表达率升高。     

成纤维细胞生长因子受体3及p53蛋白表达与膀胱癌预后关系的研究

目的 探讨膀胱癌组织中成纤维细胞生长因子受体3(FGFR3)、p53蛋白表达及与膀胱癌预后的关系.方法 免疫组织化学法检测108例膀胱癌组织和8例正常膀胱黏膜中FGFR3和p53的表达.膀胱癌患者中男60例,女48例.年龄29～87岁.TNM分期Ta～T164例、T2～T4 44例.病理分级G130例,G249例、G329例.结合临床资料分析其与膀胱癌分期、分级、复发的相关性.Kaplan-Meier法和Cox回归分析法进行生存分析. 结果 108例膀胱癌组织FGFR3阳性表达59例(54.6%),其中Ta～T1肿瘤阳性表达率75.0%,T2～T425.0%;G1 70.0%、G2 57.1%、G334.5%;p53阳性表达48例(44.4%),其中Ta～T1 25.0%、T2～T4 72.7%;G1 36.7%、G2 34.7%、G369.0%.8例正常膀胱黏膜组织FGFR3、p53表达均为阴性.组间差异均有统计学意义(P＜0.01).Spearman等级相关分析表明FGFR3与p53表达不相关(P＞0.05).Kaplan-Meier法结果表明FGFR3阳性表达组较阴性表达组、p53阴性表达组较阳性表达组有较长的复发间期(P＜0.05).单因素Cox回归分析显示FGFR3表达缺失和p53过度表达与肿瘤分级分期显著相关(P＜0.05).多因素Cox回归分析表明,p53表达是膀胱癌预后的独立影响因素(OR=0.59,P=0.04).结论膀胱肿瘤组织中FGFR3蛋白过度表达及p53蛋白表达缺失提示患者预后较好.     

膀胱尿路上皮癌MRP-1/CD9和cyclinD1的表达与肿瘤生物学行为的关系

目的:探讨MRP-1/CD9和cyclinD1的表达与膀胱尿路上皮癌生物学行为的关系。方法:应用免疫组化法检测80例膀胱尿路上皮癌组织和12例正常对照组膀胱组织MRP-1/CD9和cyclinD1的表达情况。结果:MRP-1/CD9阳性表达率膀胱癌组为51.25%,对照组为91.11%(P<0.05);Ta～T1肿瘤阳性表达率为71.42%,T2～T4为35.56%;G1肿瘤阳性表达率为78.57%,G2为43.48%,G3为31.03%,随着肿瘤浸润性和分级上升,阳性表达率逐渐下降(P<0.01,P<0.05);MRP-1/CD9阳性表达率肿瘤初发和复发者之间差异无统计学意义(P>0.05);肿瘤单发者高于多发者(P<0.05)。膀胱尿路上皮癌cyclinD1阳性表达率为53.75%,对照组为0(P<0.01);Ta～T1肿瘤阳性表达率为78.57%,T2～T4为17.65%;G1肿瘤阳性表达率为85.71%,G2为56.52%,G3为20.69%,随着肿瘤浸润性和分级升高,cyclinD1阳性表达率逐渐降低(P<0.05,P<0.05)。cyclinD1阳性表达率肿瘤初发和复发者、多发者和单发者之间差异无统计学意义(P>0.05,P>0.05)。结论:MRP-1/CD9表达与膀胱尿路上皮癌的浸润性和分级相关,其表达缺失可能是判断该肿瘤预后的一个指标;cy-clinD1较能准确地评估膀胱尿路上皮癌的生物学行为,二者对于判断膀胱癌的预后有重要的临床意义     

Expression of MIB-1, mitotic index and S-phase fraction as indicators of cell proliferation in suerficial bladder cancer

Cell proliferation of transitional cell bladder cancer (TCC) was determined by MIB-1 immunolabeling, volume-corrected mitotic index (M/V index) and S-phase fraction measurement in 207 patients with superficial (Ta-T1) bladder cancer. The results were compared to T category, WHO grade and DNA-ploidy. The MIB-1 score was related to T category (P<0.001), WHO grade (P<0.001), DNA ploidy (P<0.0001), M/V index (P<0.0001) and fraction of cells in S phase (P<0.0001). The mean MIB-1 score was 6.37% for G1, 14.59% for G2 and 28.59% for G3 carcinomas (P<0.001). The MIB-1 score for Ta tumors was 9.24% and for T1 tumors 25.34% (P<0.001). The M/V index was 3.9 for G1, 11.5 for G2 and 25.9 for G3 tumors (P<0.0001). The M/V index for Ta tumors was 6.4 and 25.3 for T1 tumors (P<0.0001). WHO grade 1 tumors had 7.7%, grade 2 tumors 13.8% and grade 3 tumors 21.8% of cells in S phase (P<0.001). Of grade 1 tumors, 97% were diploid and 3% aneuploid, and 78% of grade 2 tumors were diploid and 22% aneuploid. Of grade 3 tumors, 30% were diploid and 70% aneuploid (P<0.001). Of Ta tumors, 92% were diploid and 8% aneuploid, respectively, whereas 40% of T1 tumors were diploid and 60% aneuploid (P<0.0001). The results show that quantitative cell proliferation indices are associated with T category and WHO grade in superficial bladder cancer. The prognostic value of the S-phase fraction and mitotic index has been demonstrated in several previous analyses of prognostic factors while the value of MIB-1 score on bladder cancer prognosis remains to be established in further follow-up studies.     

Comparison of different schedules of cytostatic intravesical instillations in patients with superficial bladder carcinoma: final evaluation of a prospective multicenter study with 419 patients

In a prospective multicenter study we compared the value of various protocols of mitomycin C and doxorubicin instillation for the prevention of recurrent tumors in patients whose superficial bladder tumors (stages TA and T1) had been removed by transurethral resection. The 3-year and short-term instillation protocols were compared to each other and to a combination of 2 protocols. Evaluation after a mean followup of 28 months confirmed the value of cytostatic bladder instillation in preventing recurrence and progression of tumor in patients with superficial bladder carcinoma. There was no significant difference between the results of long-term and short-term prophylaxis; their combination achieved the best results. Doxorubicin and mitomycin yielded similar results; mitomycin was better tolerated.     

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.     

浅表性膀胱癌PD-ECGF mRNA表达的意义

目的　探讨浅表性膀胱癌中血小板衍化内皮细胞生长因子 (PD ECGF)mRNA表达的意义。方法　用逆转录多聚酶链反应 (RT PCR)分析了 2 8例浅表性膀胱癌和 6例正常膀胱粘膜的PD ECGFmRNA表达 ,并分析了PD ECGFmRNA表达与浅表性膀胱癌的固有层浸润及复发之间的关系。结果　所有标本均见不同程度的PD ECGFmRNA表达 ,粘膜固有层浸润的pT1期膀胱癌的PD ECGFmRNA表达是正常膀胱粘膜的 3 1倍 (t=2 13,P <0 0 5 ) ,是乳头状非浸润性膀胱癌 (pTa期 )的 2 2倍 (t=2 6 6 ,P <0 0 5 ) ;G3 级膀胱癌中PD ECGFmRNA表达是正常膀胱粘膜的 3 3倍(t=2 4 4 ,P <0 0 5 ) ,是G1 2 级膀胱癌的 2 5倍 (t=3 36 ,P <0 0 1)。全部病例获得随访 ,平均随访18个月 ,共复发 11例 ,复发者膀胱癌的PD ECGFmRNA水平是未复发者的 3倍 (t=4 4 9,P <0 0 1) ,用PD ECGFmRNA水平预测本组膀胱癌复发的敏感性为 81 8% ,特异性为 82 4 %。结论　PD ECGFmRNA表达不仅与浅表性膀胱癌的分化程度有关 ,而且在膀胱癌的早期浸润中起着重要作用 ,测定PD ECGFmRNA表达对判断浅表性膀胱癌的分化程度、固有层浸润与复发有一定意义。     

Analysis of factors predicting intravesical recurrence of superficial transitional cell carcinoma of the bladder without concomitant carcinoma in situ

BACKGROUND: The objective of this study was to investigate risk factors for intravesical recurrence in patients with superficial bladder cancer without concomitant carcinoma in situ (CIS). METHODS: In this series, we analyzed data from patients with newly diagnosed superficial Ta or T1 transitional cell carcinoma (TCC) of the bladder without concomitant CIS who underwent complete transurethral resection (TUR) without any adjuvant intravesical instillation therapies. Multivariate analysis was used to determine significant risk factors affecting intravesical recurrence after TUR. Differences in clinicopathological features between primary and recurrent tumors were also characterized. RESULTS: Among 341 patients undergoing TUR of Ta or T1 bladder cancer, 187 diagnosed as having concomitant CIS and/or treated with adjuvant intravesical therapy were excluded, and the remaining 154 were evaluated. Intravesical recurrence was detected in 64 of the 154 patients, showing a 5-year recurrence-free survival rate of 58.3%. Among several factors examined, only tumor size was significantly associated with intravesical recurrence. Multivariate analysis identified tumor size as an independent predictor for intravesical recurrence irrespective of other parameters including age, gender, multiplicity, growth pattern, grade and stage. Recurrent tumors were significantly smaller and of a lower grade and lower stage than primary tumors, despite the absence of differences in growth pattern and the multiplicity between them. CONCLUSIONS: These findings suggest that primary tumor size could be used as a potential risk factor for predicting intravesical recurrence following TUR of superficial TCC of the bladder without concomitant CIS, and that the pathological characteristics of recurrent tumors are more favorable than those of primary tumors.     

Therapy of superficial bladder carcinomas

Treatment of superficial bladder carcinoma was derived by several large randomized trials. This group of cancers is stratified by differentiation grade and stage in three groups of different risk profiles (Ta G1-2 vs. T1 G1-2 vs. Tis/T1 G3). Standard therapy is fractionated transurethral resection (TUR). Adjuvant therapy after transurethral resection is not indicated in primary Ta G1-2 tumors because there is a low recurrence rate and no risk of tumor progression. The recurrence rate can be decreased up to 15% in recurrent Ta or T1 G1-2 tumors by intravesical therapy with mitomycin C (20 mg/instillation) or adriamycin (50 mg/instillation). Therapy should be limited to early (within 24 h post-TUR) and short-term treatment (4 x weekly, 5 x monthly). Alternatively, patients can be treated by intravesical BCG (strain Connaught or strain RIVM). Maintenance therapy is advantageous according to recurrence rate. Tumors with great malignant ability (Tis or T1 G3) will be treated initially with adjuvant BCG. Patients who fail are candidates for radical cystectomy within 3-6 months after initial diagnosis. There is no need - except in clinical trials - for the administration of unverified or not admitted drugs. Copyright Copyright 1999 S. Karger AG, Basel     

Cytostatic intravesical instillation in patients with superficial bladder carcinoma for the prevention of recurrent tumors

The value of various protocols of mitomycin C and adriamycin instillation for the prevention of recurrent tumors in patients whose superficial bladder tumors (TA, T1) had been removed by transurethral resection was compared in a prospective multicenter study. Three-year and short-term instillation protocols were compared with each other and with the combination of the two. Evaluation after a mean follow-up of 20 months confirmed our previous conclusion of the great value of cytostatic bladder instillation to prevent recurrent tumors and tumor progression in patients with superficial bladder carcinoma. There is no significant difference between long-term and short-term prophylaxis, but combination has achieved the best results. Similar results were obtained with adriamycin and mitomycin but adriamycin was less well tolerated.