cyclinD_1表达与膀胱移行细胞癌生物学行为关系的研究

目的 :检测 cyclin D1 在膀胱移行细胞癌 (TCC)中的表达 ,探讨其与该肿瘤生物学行为的关系。方法 :应用免疫组化 SP法检测 45例膀胱 TCC和 12例正常膀胱 cyclin D1 组织的表达。结果 :膀胱 TCC组 cyclin D1 阳性表达率为 5 5 .5 6 % ,对照组无表达 ;临床分期 T0 ～ T1 为 78.5 % ,T2 ～ T4为 11.76 % ;肿瘤分级 G1 为 85 % ,G2 为46 .6 7% ,G3为 10 % ,随着肿瘤分期分级上升 ,阳性表达率逐渐升高 ;但在肿瘤初发和复发及单发和多发之间差异无显著性。结论 :cyclin D1 在膀胱 TCC形成的早期起重要的作用 ;在评估膀胱 TCC的生物学行为方面有着重要的临床意义     

E—cadherin和α—catenin在膀胱移行细胞癌中的表达及意义

[目的]研究钙粘附分子（E-cadherin,E-cad)和α-连接蛋白在膀胱移行细胞癌中的表达及其临床意义。[方法]正常膀胱粘膜E-cad呈正常表达，96例膀胱移行细胞癌中E-cad及α-cat的异常表达率分别为44.8%（43/96）和58.3%(56/96)。两者之间具有显著相关性。E-cad及α-cat的异常表达率与肿瘤的病理分级、临床分期、复发及生存率显著相关。[结论]E-cad及α-cat的异常表达在膀胱移行细胞癌的恶性进展过程中起重要作用。可作为判断肿瘤恶性程度及复发预后的分子生物学指标。     

非小细胞肺癌中上皮钙粘附素的表达及其意义

目的研究上皮钙粘附素(epithelialcadherin,E-cad)在非小细胞肺癌(non-smallcelllungcancer,NSCLC)中的表达,探讨E-cad与NSCLC的组织类型、病理分级、TNM分期及淋巴结转移的关系。方法应用免疫组织化学SABC法检测65例原发性NSCLC,20例癌旁组织中E-cad蛋白的表达水平。结果20例正常肺组织均阳性表达,且均匀分布于膜表面。NSCLC中E-cad表达不均匀,阳性率为32.3%,与正常组比较差异有显著性(P<0.05)。但与组织类型无关(P>0.05),与病理分级、TNM分期及淋巴结转移显著相关(P<0.05)。结论E-cad与NSCLC的发生发展呈显著负相关,低表达者预示预后不良。     

cyclinD1表达与膀胱移行细胞癌生物学行为关系的研究

目的：检测cyclinD1在膀胱移行细胞癌（TCC）中的表达，探讨其与该肿瘤生物学行为的关系，方法：应用免疫组化SP法检测45例膀胱TCC和12例正常膀胱cyclinD1组织的表达，结果：膀胱TCC组cyclinD1阳性表达率为55．56％，对照组无表达；临床分期T0－T1，为78．5％，T2－T4为11．76％；肿瘤分级G1为85％，G2为46．67％，G3为10％，随着肿瘤分期分级上升，阳性表达率逐渐升高，但在肿瘤初发和复发及单发和多发之间差异无显著性。结论：cyclinD1在膀胱TCC形成的早期起重要的作用。在评估膀胱TCC的生物学行为方面有着重要的临床意义。     

子宫内膜癌中E-cad PTEN蛋白表达及其临床意义

目的:探讨上皮型钙粘素(E-cad)和PTEN在子宫内膜癌中的蛋白表达及临床意义.方法:应用免疫组织化学SP法,检测37例正常子宫内膜(NE),40例非典型增生内膜(AHE)和72例癌性内膜(CE)中E-cad、PTEN的蛋白表达,并结合临床指标、预后进行分析.结果:在NE、AHE和CE中E-cad表达阳性率为100%(37/37)、70.00%(28/40)和47.22%(34/72);PTEN表达阳性率为100%(37/37)、77.50%(31/40)和48.61%(35/72).E-cad的表达与内膜癌患者临床分期、浸润深度和病理分级相关.临床Ⅰ Ⅱ期和浸润深度≤1/2的E-cad表达阳性率高(P＜0.05),病理分级G1、G2、G3表达逐渐下降(P＜0.05).E-cad高表达组5年生存率比低表达组高(P＜0.05).PTEN的表达与临床分期和病理分级相关,Ⅰ Ⅱ期组的PTEN表达阳性率低于Ⅲ Ⅳ期;随着肿瘤细胞的去分化,PTEN表达降低(P＜0.05);PTEN高表达组的5年生存率高于低表达组(P＜0.05).结论:PTEN和E-cad均在子宫内膜癌的发生、发展中起重要作用,与预后密切相关.     

肿瘤细胞增生活性与膀胱移行细胞癌生物学行为关系的研究

目的 :检测 Ki- 6 7抗原在膀胱移行细胞癌 (TCC)中的表达 ,研究肿瘤增生活性与肿瘤生物学行为的关系。方法 :应用免疫组化 SP法检测 45例膀胱 TCC和 12例正常膀胱组织 Ki- 6 7抗原的表达。Ki- 6 7标记指数 (Ki- 6 7L I)指染色阳性细胞占全部细胞的百分数。其分级标准为 :无阳性细胞为— ,阳性细胞 <2 5 %为 ,≥ 2 5 %、<5 0 %为 ,≥ 5 0 %、<75 %为 ,≥ 75 %为 。结果 :Ki- 6 7抗原阳性表达率膀胱 TCC组为 48.47% ,对照组为 8.33% (P=0 .0 11) ;临床分期 Ta～ T1 为 35 .71% ,T2 ～ T4为 76 .47% ,病理分级 G1 为 2 5 % ,G2 为 5 3.33% ,G3 为 90 %。随着肿瘤分期分级升高 ,Ki- 6 7L I逐渐上升 (P=0 .0 0 4,P=0 .0 0 1)。Ki- 6 7L I肿瘤复发、多发者明显高于初发、单发者 (P=0 .0 14,P=0 .0 34 )。结论 :细胞无限增生是肿瘤形成的重要原因 ,Ki- 6 7L I能准确地评估膀胱 TCC的生物学行为 ,可作为膀胱 TCC有重要意义的肿瘤标志物     

膀胱癌组织中端粒酶活性的检测及其意义

目的 研究端粒酶与膀胱移行细胞癌（TCC）生物学行为的关系。方法 方法 采用端粒酶重复序列扩增法及酶联免疫吸附性检测58例TCC组织、10例癌旁膀胱粘膜及10例正常膀胱粘膜组织的端粒酶活性。结果 TCC组织端粒酶阳性率为86．2（50／58）,不同病理分级、临床分期之间无显著性差异（P＞0．05）;癌旁组织中只有1例端粒酶阳性;正常组织中端粒酶均为阴性。结论 TCC组织中端粒酶活性阳性率明显高于正常膀胱粘膜组织及癌旁膀胱粘膜组织。各病理分级和临床分期之间端粒酶活性虽然无显著性差异（P＞0．05）,但端粒酶活性的强弱分布不同。端粒酶活性可作为TCC早期诊断、鉴别诊断及预测复发的肿瘤标志物之一。     

Caspase-3与Bcl-2蛋白在膀胱移行细胞癌中的表达及意义

背景和目的:肿瘤的发生是细胞异常增生和凋亡不足的结果。以往研究认为凋亡的发生与Caspase-3和Bcl-2蛋白有密切的联系。本研究拟通过检测Caspase-3和Bcl-2蛋白在膀胱移行细胞癌中的表达,探讨其在膀胱移行细胞癌发生、发展中的意义。方法:采用免疫组织化学(SP)法,对52例膀胱移行细胞癌组织和10例正常膀胱粘膜组织中的Caspase-3及Bcl-2蛋白表达情况进行检测。结果:膀胱移行细胞癌组织中的Caspase-3蛋白表达率(53.8%,28/52)明显低于正常膀胱粘膜组织(90.0%,9/10),Caspase-3的蛋白表达与膀胱移行细胞癌的病理分级有关(P<0.05),但与临床分期没有明显的联系;膀胱移行细胞癌组织中的Bcl-2蛋白表达率(51.9%,27/52)明显高于正常膀胱粘膜组织(20.0%,2/10),且Bcl-2蛋白表达情况与病理分级、临床分期均无关(P>0.05)。在正常膀胱粘膜中Caspase-3与Bcl-2的蛋白表达呈负相关(rs=-0.659,P<0.01)。结论:Caspase-3蛋白的高表达与Bcl-2蛋白的低表达在膀胱癌的发生和细胞凋亡的调控方面可能起着重要作用。     

IGF-Ⅰ和IGF-ⅠR在膀胱癌组织中表达的意义

背景与目的:胰岛素样生长因子(insulin-likegrowthfactors,IGFs)是一类具有促进细胞增殖、分化等多种生物学活性的多肽生长因子,研究表明其参与多种恶性肿瘤的发生、发展过程。本研究检测IGF-Ⅰ及其受体IGF-ⅠR和增殖细胞核抗原(proliferationcellnuclearantigen,PCNA)在正常膀胱组织和膀胱癌组织中的表达,评价IGF-Ⅰ和IGF-ⅠR的临床意义。方法:应用免疫组织化学方法检测IGF-Ⅰ、IGF-ⅠR和PCNA在88例膀胱癌和12例正常膀胱组织中的表达,同时对IGF-Ⅰ和IGF-ⅠR表达与膀胱癌病理分级、临床分期、预后及PCNA表达之间的关系进行分析。结果:膀胱癌组织中IGF-Ⅰ和IGF-ⅠR阳性率分别为73.9%、59.1%,均显著高于正常膀胱组织的33.3%、16.7%(P<0.05)。膀胱癌中两者呈相关表达且均与PCNA指数密切相关(P<0.05)。IGF-Ⅰ表达与肿瘤复发之间关系密切(P<0.05),IGF-ⅠR表达则与肿瘤分级、分期和复发关系密切(P<0.05)。结论:IGF-Ⅰ与肿瘤复发有关,IGF-ⅠR表达与肿瘤分级、分期和复发有关。     

腺样囊性癌钙粘蛋白的增殖细胞核抗原表达的临床意义

背景与目的:腺样囊性癌(adenoidcysticcarcinoma,ACC)的临床经过常表现为治疗后复发和转移。目前尚无确切的预后判断指标。本文探讨ACC上皮细胞粘附分子钙粘蛋白(E-cadherin,E-cad)和增殖细胞核抗原(proliferatingcellnuclearantigen,PCNA)表达与预后的关系。方法:应用免疫组化染色方法对34例腺样囊性癌E-cad和PCNA的表达进行检测。结果:实体型ACC患者5年生存率明显低于筛状型和管状型患者(P<0.01)。临床分期与ACC复发转移(P<0.01)及患者术后5年生存率显著相关(P<0.01)。E-cad低表达者(占50.0%)在复发、转移和术后生存时间小于5年者多见(P<0.05)。PCNA高表达组的复发转移率明显高于低表达组(P<0.005),前者术后5年生存率则显著低于后者(P<0.005)。E-cad与PCNA在ACC中的表达显著相关(P<0.005)。结论:E-cad、PCNA的表达及临床分期可作为ACC判断预后的指标;E-cad和PCNA可能在ACC恶性进展中起协同作用。     

环氧化酶-2 在膀胱癌组织及尿脱落细胞中的表达和意义

 目的 探讨COX-2在膀胱癌组织中的表达，了解尿脱落细胞COX-2表达在膀胱癌早期诊断中的价值。方法 应用免疫组化技术检测48例膀胱移行细胞癌组织、免疫细胞化学技术检测40例膀胱移行细胞癌患者和30例非肿瘤患者尿脱落细胞COX-2的表达。结果 膀胱移行细胞癌组织COX-2阳性表达率为72．9％，对照组正常膀胱黏膜无表达。COX-2的表达与膀胱癌临床分期显著相关(P<0．05)，不同病理分级膀胱癌的表达差别无显著性意义。非肿瘤患者尿脱落细胞无COx-2表达，膀胱癌尿脱落细胞COX-2免疫细胞化学检测阳性率为67．5％，明显高于常规尿细胞学的37．5％(P<0．05)，尤其对于G1级和Ta～T1期的低级、早期肿瘤，尿脱落细胞COX-2免疫细胞化学检测与常规尿细胞学检查相比，具有显著性意义(P<0．05)。结论 COX-2在膀胱移行细胞癌的发生发展中起重要作用，与肿瘤的浸润、转移相关。尿脱落细胞COX-2表达检测特异性高，可作为早期诊断膀胱癌的一种标志物。     

Clinical implications of the expression of epidermal growth factor receptors in human transitional cell carcinoma.

To evaluate the distribution and density of epidermal growth factor (EGF) receptors (EGF-Rs) on urothelium, immunohistological studies using a monoclonal antibody to the binding portion of the human EGF-R were performed on frozen specimens of normal urothelium (N = 20), urothelium from patients with nonurothelial urological malignancies (N = 15) and inflammatory diseases (N = 8), low grade superficial transitional cell carcinomas (TCC) (N = 13), high grade superficial or invasive TCC (N = 28), and endoscopically normal appearing urothelium from patients with low grade superficial (N = 5) or high grade (N = 21) TCC elsewhere in the bladder (or ipsilateral renal pelvis/ureter). EGF-Rs are found only on the basal layer of epithelial cells (with scattered representation on intermediate cells) in 95% of normal urothelial specimens and 100% of pathological specimens without urothelial malignancy. Alternatively, 92.3% of specimens of low grade superficial TCC and 100% of high grade TCCs had EGF-Rs richly expressed on the superficial as well as the deeper layers of urothelium. This "malignant" distribution of EGF-Rs was also found on all specimens of endoscopically normal appearing urothelium in patients with TCC elsewhere. The density of EGF-Rs correlated closely with tumor grade on both "premalignant" and frankly neoplastic urothelium. We conclude that the expression of EGF-Rs on urothelium favors the interaction of premalignant and malignant tissue with urinary EGF. To determine if altering the physiochemical environment of urine could interfere with this interaction, the effects of pH on the binding of and growth responses to EGF were assessed on four human TCC cell lines. Scatchard plots demonstrated that varying pH from 5.0 to 7.5 did not significantly change the total number of receptors, but EGF-R affinity was reduced approximately 20-fold as pH decreased from 7.5 to 5 in each TCC target. Similarly, significant growth stimulation by EGF at pH 7.5 was abrogated at pH less than or equal to 7.0 while growth rates in the absence of EGF remained unchanged at lower pHs. It thus appears that urinary acidification may hold promise in the management and prevention of recurrent bladder cancer.     

Prostate stem cell antigen is overexpressed in human transitional cell carcinoma.

Prostate stem cell antigen (PSCA), a homologue of the Ly-6/Thy-1 family of cell surface antigens, is expressed by a majority of human prostate cancers and is a promising target for prostate cancer immunotherapy. In addition to its expression in normal and malignant prostate, we recently reported that PSCA is expressed at low levels in the transitional epithelium of normal bladder. In the present study, we compared the expression of PSCA in normal and malignant urothelial tissues to assess its potential as an immunotherapeutic target in transitional cell carcinoma (TCC). Immunohistochemical analysis of PSCA protein expression was performed on tissue sections from 32 normal bladder specimens, as well as 11 cases of low-grade transitional cell dysplasia, 21 cases of carcinoma in situ (CIS), 38 superficial transitional cell tumors (STCC, stages T(a)-T(1)), 65 muscle-invasive TCCs (ITCCs, stages T(2)-T(4)), and 7 bladder cancer metastases. The level of PSCA protein expression was scored semiquantitatively by assessing both the intensity and frequency (i.e., percentage of positive tumor cells) of staining. We also examined PSCA mRNA expression in a representative sample of normal and malignant human transitional cell tissues. In normal bladder, PSCA immunostaining was weak and confined almost exclusively to the superficial umbrella cell layer. Staining in CIS and STCC was more intense and uniform than that seen in normal bladder epithelium (P < 0.001), with staining detected in 21 (100%) of 21 cases of CIS and 37 (97%) of 38 superficial tumors. PSCA protein was also detected in 42 (65%) of 65 of muscle-invasive and 4 (57%) of 7 metastatic cancers, with the highest levels of PSCA expression (i.e., moderate-strong staining in >50% of tumor cells) seen in 32% of invasive and 43% of metastatic samples. Higher levels of PSCA expression correlated with increasing tumor grade for both STCCs and ITCCs (P < 0.001). Northern blot analysis confirmed the immunohistochemical data, showing a dramatic increase in PSCA mRNA expression in two of five muscle-invasive transitional cell tumors when compared with normal samples. Confocal microscopy demonstrated that PSCA expression in TCC is confined to the cell surface. These data demonstrate that PSCA is overexpressed in a majority of human TCCs, particularly CIS and superficial tumors, and may be a useful target for bladder cancer diagnosis and therapy.     

凋亡相关基因Fas、FasL和bcl-2在膀胱移行细胞癌中的表达

目的　研究凋亡相关基因Fas、FasL和bcl-2 ,在膀胱移行细胞癌 (TCC )中的表达情况 ,并探讨其临床意义。方法　采用S -P免疫组化方法 ,检测 67例TCC及 12例正常膀胱组织中Fas、FasL和bcl -2蛋白的表达。结果　在TCC和正常膀胱组织中FasL蛋白阳性率分别为 5 6.7%和 0 ,两者有非常显著性差异 (P <0 .0 1) ,而Fas和bcl -2蛋白在TCC和正常膀胱组织中的表达无显著性差异 (P >0 .0 5 )。Fas和bcl -2蛋白表达阳性率在TCC不同病理分级、分期有非常显著性差异 (P <0 .0 1)。FasL蛋白表达随着TCC分级、分期的增加 ,呈降低趋势 ,但无显著性差异 (P >0 .0 5 )。结论　Fas/FasL系统异常可能是TCC发生发展过程中免疫逃逸的重要因素 ;在TCC发生以及在低分化和浸润性TCC中 ,Fas/FasL基因介导的细胞凋亡可能被bcl -2基因的过度表达所抑制 ;Fas和bcl -2基因表达可作为监测TCC恶性程度的重要指标     

Expression of matrix metalloproteinases in human transitional cell carcinoma of the urinary bladder

Matrix metalloproteinases (MMPs) are associated with invasion and metastasis of several human malignant tumors. Especially so MMP-7, as it is mainly produced by the actual cancer cells. However, the expression of MMP-7 in transitional cell carcinoma (TCC) of the urinary bladder has not been previously investigated. We examined expressions of MMP-7 and MMP-2 in TCC, and compared them with clinicopathological characteristics in TCCs. Tumor samples from 20 patients with TCC of the urinary bladder who had surgery performed at the Osaka City University Medical School Hospital were immunohistochemically stained. Expression of MMP-2 was significantly stronger in advanced stage and high grade tumors than in low stage and low grade tumors. MMP-7 was also expressed in TCC, having a tendency to be more strongly expressed in high than in low grade tumors. However, there was no significant difference of MMP-7 expression between advanced and low stages. This increased expression of MMP-7 in high grade TCC of the urinary bladder may be associated with tumor invasion and metastasis.     

人膀胱移行细胞癌内的16／18型人乳头状瘤病毒感染

目的 探讨人膀胱移行细胞癌与高危型人乳头瘤病毒感染的关系。方法 采用聚合酶链式反应（ＰＣＲ法）检测１１２例膀胱移行细胞组织（包括７５例石蜡包埋组织和３７例手术切除组织）和７例正常膀胱粘膜组织的ＨＰＶ－１６／１８感染率及ＨＰＶ－１６／１８感染与膀胱移行细胞癌病理分极及临床分期的关系。同时检测了２４例膀胱癌病人尿液沉淀中ＨＰＶ阳性率。结果 膀胱移行细胞癌的ＨＰＶ－１６／１８的总感染率为６２．５０％（７     

Prognostic impact of plasminogen activator inhibitor type 1 expression in bladder cancer

BACKGROUND:

Recent studies have demonstrated a poor prognosis for patients who have altered expression of plasminogen activator inhibitor type 1 (PAI‐1) in several cancer types. The objective of the current study was to investigate the prognostic impact of PAI‐1 on patients with transitional cell carcinoma (TCC) of the urinary bladder.

METHODS:

PAI‐1 expression was quantified using real‐time polymerase chain reaction in 91 TCCs and in 6 normal tissue specimens. PAI‐1 concentrations were analyzed by enzyme‐linked immunoadsorbent assay in plasma from 104 patients and 10 controls and in urine from 244 patients and 74 controls. PAI‐1 expression was evaluated immunohistochemically in paraffin‐embedded tissues (94 tumor samples and 10 adjacent normal tissue samples). The results were analyzed in relation to clinical features and follow‐up.

RESULTS:

Significantly higher PAI‐1 levels were detected in tissue and plasma samples, but not in urine, from patients with bladder cancer compared with controls (P = .001 and P = .008, respectively). Elevated gene expression and plasma protein concentrations were independent of tumor stage and grade. Immunostaining revealed a subgroup of patients with single tumor cells that strongly expressed PAI‐1. These patients' survival was significantly shorter, and their clinical presentation was correlated significantly with lymph node‐positive disease.

CONCLUSIONS:

PAI‐1 gene expression in tissues and plasma protein levels were elevated in patients with TCC compared with controls. PAI‐1 gene or protein expression was not associated with the clinical characteristics of bladder TCC. Although the assessment of PAI‐1 expression in plasma or urine may not serve as an independent predictor of prognosis in patients with TCC, the immunohistochemical detection of single PAI‐1–positive cells may serve as a predictor of survival and a possible indicator of metastasis. Cancer 2010. © 2010 American Cancer Society.