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。     

尿中血管内皮生长因子表达与膀胱移行细胞癌诊断及术后监测

目的探讨尿中血管内皮生长因子(VEGF)表达与膀胱移行细胞癌的关系,以及尿VEGF做为瘤标的价值.方法用抗体夹心ELISA法测量58例研究对象的尿VEGF,并与尿细胞学检查比较(双盲法).其中28例为膀胱移行细胞癌,每3个月随访1次,6例复发.结果尿VEGF在膀胱癌组高于非膀胱癌组(P＜0.001);G1级癌分别低于G2、G3级癌(P＜0.05),在早期复发组高于未复发组(术前)(P＜0.05),尿VEGF诊断实验的特异度和灵敏度分别为93.3%、85.7%.结论尿VEGF水平可反映膀胱癌的预后、复发;尿VEGF做为诊断和术后监测瘤标有较高价值,优于尿细胞学检查.     

膀胱癌抗原在膀胱移行细胞癌诊断中的价值

目的评价膀胱癌抗原(UBC)对膀胱移行细胞癌(BTCC)的诊断价值.方法采用ELISA法对89例BTCC及108例泌尿系非移行细胞癌(TCC)患者的尿UBC进行检测,并同时行尿脱落细胞学检查.结果 BTCC患者尿UBC均值为30.5 μg/L,与泌尿系非TCC患者8.2μg/L的均值比较,差别有显著性意义(P＜0.01).尿UBC(以8.4μg/L为最适临界值)和尿细胞学诊断BTCC的敏感性分别为75.3%和16.9%,特异性分别为77.8%和100%,两者差别均有显著性意义(P＜0.01).结论尿UBC检测对BTCC的诊断是一种较为敏感、特异且无创的方法,敏感性明显优于尿细胞学,但临床上不能完全替代尿细胞学检查.     

人膀胱癌细胞角蛋白20 mRNA表达的研究

目的　评估细胞角蛋白 2 0mRNA(CK2 0mRNA)是否可以作为膀胱癌临床诊断的一种有用标志物。方法　对 84例肉眼血尿患者的尿液进行尿脱落细胞学及CK2 0mRNA标记物RT/PCR检测。分析参数包括肿瘤数目、大小及WHO分级 ,术前或活检前尿脱落细胞学和CK2 0mRNA标志物。结果　病理活检证实 2 2例移行细胞癌中 ,CK2 0mRNA 18例为阳性 ,4例阴性 ;6 2例非膀胱癌患者中 ,CK2 0mRNA标志物 2例假阳性。与尿脱落细胞学比较 ,CK2 0mRNA标志物对膀胱移行细胞癌诊断的特异性和阳性预报值更高 ,分别为 96 .8%比 77.4 % (U =3.2 1,P <0 .0 1) ,90 %比 5 1.7% (U =2 .81,P <0 .0 1) ;但两者在敏感性和阴性预报值间无显著性差异 (U值分别为 :1.0 4和 1.2 1,P >0 .0 5 )。CK2 0mRNA表达与肿瘤分级间无明显相关性。结论　通过RT/PCR方法检测CK2 0mRNA是诊断膀胱移行细胞癌的一种良好生物标志物 ,其特异性明显优于尿脱落细胞学。     

膀胱移行细胞癌尿液脱落细胞中Livinα的表达及意义

目的:研究膀胱移行细胞癌(BTCC)尿液脱落细胞中Livinα的表达及意义.方法:留取49例BTCC患者、21例其他系统疾病患者和15例正常健康成人的新鲜尿液,离心收集脱落细胞,以逆转录多聚酶链反应(RT-PCR)检测尿液脱落细胞中Livinα的表达,并行尿脱落细胞学检查.结果:49例BTCC患者尿脱落细胞中有40例检测出Livinα表达,而21例其他系统疾病患者和15例正常健康成人的尿脱落细胞中均未检测出Livinα的表达.以RT-PCR 方法检测膀胱癌患者尿液脱落细胞中Livinα的敏感性为81.6%,特异性为100%.尿脱落细胞学检查的敏感性和特异性为16.3%和100%,两种方法之间存在显著性(P<0.05).结论:初步的试验结果显示,RT-PCR法检测膀胱癌患者尿液脱落细胞中Livinα的方法比细胞学检查灵敏度高,可能成为诊断膀胱癌的无创性方法.     

细胞角蛋白20对膀胱癌早期诊断的前瞻性研究

目的：评估细胞角蛋白20（CK20）标志物作为膀胱癌早期诊断及临床监测的价值。方法：对62例患者的尿液进行尿脱落细胞学及CK20标志物免疫荧光检测的前瞻性研究。分析参数包括肿瘤数目、大小及WHO分级，术前或活检前尿脱落细胞学和CK20标志物。结果：病理活检证实15例移行细胞癌中，CK20为13例阳性，2例阴性；47例非膀胱癌中，CK20标志物2例假阳性。与尿脱落细胞学比较，CK20标志物对膀胱移行细胞癌诊断的特异性和阳性预报值更高，分别为96．0％比82．5％（U＝2．18，P＜0．05），86．7％比52．4％（U＝2．16，P＜0．05）；但两者在敏感性和阴性预报值间无显著性差异（U值分别为：0．91和1．02，P＞0．05）。CK20表达与肿瘤分级间无明显相关性。结论：CK20是诊断膀胱移行细胞癌的一种良好标志物，其特异性明显优于尿脱落细胞学。     

尿液中膀胱肿瘤标志物检测的研究进展

膀胱癌是泌尿系统最常见的恶性肿瘤之一,易复发,发病率正逐年增高.目前膀胱镜检查和尿细胞学检查仍是膀胱移行细胞癌(bladder transitional cell carcinoma,BTCC)诊断和随访的金标准.由于膀胱镜检查会带给患者创伤且检测费用昂贵,同时细胞学检查的敏感性低.随着分子生物学技术的发展,许多膀胱肿瘤标志物被逐步发现,因此选择高敏感性和特异性的膀胱肿瘤标志物用于肿瘤的早期诊断和治疗将具有重要的临床应用价值.本文就近年来膀胱肿瘤标志物检测的研究进展作一综述.     

尿液核基质蛋白22在膀胱移行上皮癌筛检中的价值

目的：评价尿核基质蛋白22(NMP22)在膀胱移行上皮癌筛检中的意义。方法：采用酶联免疫法检测28例膀胱移行上皮癌、25例泌尿系良性疾病和10例泌尿系非移行上皮癌患者尿NMP22水平，并与尿脱落细胞学检查进行比较。结果：膀胱移行上皮癌患者尿NMP,,中位值为66．5u／ml，明显高于泌尿系良性疾病和非移行上皮癌，与肿瘤分期、分级、数目无关，以10u／ml为临界，诊断膀胱癌敏感性为85．7％，特异性为60％，尿脱落细胞学检查敏感性为32．1％，特异性为100％。结论：尿NMP22检测膀胱移行上皮癌敏感性、特异性均较高，可用于膀胱移行上皮癌的筛选和术后随访。     

Survivin分子信标诊断膀胱肿瘤的临床应用研究

目的:探讨分子信标检测尿脱落细胞Survivn mRNA的可行性,寻找一种能够早期诊断膀胱肿瘤的方法。方法:分子信标检测膀胱肿瘤5637、J82细胞Survivin mRNA的表达,并通过Western bolt方法验证,并对35例膀胱移行细胞癌患者和35名正常健康成人行分子信标检测尿脱落细胞,Western bolt检测组织中的Survivin含量,同时行尿脱落细胞学检查。结果:Survivin分子信标检测肿瘤细胞内的Survivin表达且具有高特异性。以随机100个细胞中60个以上的细胞为阳性做为阳性标准,确定MB-cy3的阳性率为80%(28/35),特异性为77.1%(27/35);Western bolt检测的阳性率为71.4%(25/35)。两种实验方法对细胞和蛋白质中Survivin的检测结果具有一致性。尿脱落细胞学的敏感性为28.6%(10/35),特异性为100.00%(35/35)。结论:使用分子信标检测尿液脱落细胞中Survivin mRNA具有可行性,分子信标有可能成为在膀胱肿瘤的早期临床诊断和术后随访的有效工具。     

尿液核基质蛋白22测定诊断尿路移行细胞癌

背景与目的:目前尿路移行细胞肿瘤缺乏有效的无创监测方法。近年来发现的核基质蛋白22(nuclearmatrixprotein22,NMP22)能有效地诊断膀胱移行细胞癌。本研究探讨NMP22作为一个新的尿液中的肿瘤标志物在尿路移行细胞癌筛选诊断中的意义及其影响因素。方法:采用酶联免疫吸附试验NMP22试剂盒,对包括29例尿路移行细胞癌在内的87例泌尿系疾病患者尿液进行的NMP22测定。有尿路感染的患者排除在外。结果:以>10u/ml为阳性判断标准,NMP22对尿路移行细胞癌的敏感性和特异性分别为86.2%和94.3%(以泌尿系良性疾病作对照),远优于尿细胞学检查(86.2%vs42.3%,P<0.001)。引起假阳性的主要因素有尿路感染、泌尿系其他恶性肿瘤、肠道膀胱和肾结石等。结论:尿NMP22是一个较好的肿瘤标志物,可以替代尿液细胞学检查成为尿路移行细胞癌诊断的良好指标。     

The role of urinary cytology for detection of bladder cancer.

PURPOSE: The aim of the present study was to test the value of urinary cytology in the diagnosis of bladder cancer. MATERIALS AND METHODS: One thousand three hundred and eighty voided urine and bladder wash specimens of 495 patients were evaluated by urinary cytology. All patients then underwent transurethral resection of suspicious bladder areas if cystoscopy and/or preceding biopsy were positive. Statistical differences were analysed using the two-sided Fisher's exact test and Cochran's test (p<0.05). RESULTS: In 495 patients including 142 patients with bladder cancer urinary cytology revealed a sensitivity of 38.0% and a specificity of 98.3% with a positive and negative predictive value of 90.6 and 78.6, respectively. Sensitivity increased significantly with malignancy grade (p<0.05). In high grade tumours sensitivity improved from initial 52.2% up to 78.3% after the third sample. In sensitivity and specificity of voided urine and barbotage washing samples no significant difference was detected. CONCLUSIONS: Urinary cytology has its place as an additive diagnostic tool to cystoscopy. None of the currently available urinary markers can replace cystoscopy but are helpful for specific diagnostic problems.     

The diagnostic efficacy of urinary TGF-beta1 and VEGF in bladder cancer: comparison with voided urine cytology

The purpose of this study was to evaluate the diagnostic efficacy of urinary transforming growth factor-beta1 (TGF-beta1) and vascular endothelial growth factor (VEGF) in comparison with voided urine cytology in the detection of bladder cancer. This study included 120 patients with bladder cancer, 54 patients with benign urological disorders and 55 healthy volunteers. Urine supernatant was used for estimation of TGF-beta1 and VEGF by ELISA. VEGF was detected by Western blot (WB) analysis in the urine supernatant of randomly selected bladder cancer patients. The urine sediment was used for cytology. There was a statistically significant difference in the median levels of TGF-beta1 (P=0.002) and VEGF (P=0.000) between the control, benign and malignant groups. The concordance rate of VEGF ELISA with VEGF WB was 96.3%. The overall sensitivity and specificity were 70.8% and 90.8% for voided urine cytology, 71.6% and 59.6% for TGF-beta1, and 76.7% and 61.5% for VEGF. The combined use of voided urine cytology with TGF-beta1 and VEGF improved the sensitivity up to 94.9%, although it lowered specificity to 62.0%. There was a significant association between positivity rate of TGF-beta1 and positive urine cytology samples (P=0.023). Median level and positivity rate of VEGF were significantly associated with early stage (I, II) of bladder carcinoma (P=0.01 and 0.025, respectively). Our data indicate that urinary TGF-beta1 and VEGF had higher sensitivities compared to voided urine cytology. Moreover, the combined sensitivity of voided urine cytology with TGF-beta1 and VEGF together was higher than sensitivity of voided urine cytology alone in detection of bladder cancer.     

Diagnostic Evaluation of Urinary Angiogenin (ANG) and Clusterin (CLU) as Biomarker for Bladder Cancer

Bladder carcinoma is an important worldwide health problem. Both cystoscopy and urine cytology used in detecting bladder cancer suffer from drawbacks where cystoscopy is an invasive method and urine cytology shows low sensitivity in low grade tumors. This study validates easier and less time-consuming techniques to evaluate the value of combined use of angiogenin and clusterin in comparison and combination with voided urine cytology in the detection of bladder cancer patients. This study includes malignant (bladder cancer patients, n?=?50), benign (n?=?20) and healthy (n?=?20) groups. The studied groups were subjected to cystoscopic examination, detection of bilharzial antibodies, urine cytology, and estimation of urinary angiogenin and clusterin by ELISA. The overall sensitivity and specificity were 66 and 75 % for angiogenin, 70 and 82.5 % for clusterin and 46 and 80 % for voided urine cytology. Combined sensitivity of voided urine cytology with the two studied biomarkers was 88 % which is higher than the combined sensitivity of both markers alone (82 %) and that of the cytology with each marker (76 and 80 %) for angiogenin and clusterin respectively. In conclusion, combined use of the cytology with the studied biomarkers can improve the sensitivity for detecting bladder cancer, and may be very useful in monitoring the effectiveness of antiangiogenic and apoptotic therapies in bladder cancer.     

Diagnostic value of fibronectin and mutant p53 in the urine of patients with bladder cancer: impact on clinicopathological features and disease recurrence

Development of new methods for bladder cancer detection is required because cystoscopy is invasive, and voided urine cytology (VUC) has low sensitivity. The aim of this study was to evaluate the diagnostic performance of urinary fibronectin and mutant p53 in comparison with VUC in the detection of bladder cancer. This study included 100 patients diagnosed with bladder cancer, 93 patients with benign urological disorders and 47 healthy volunteers. The urine supernatant was used for determination of fibronectin by ELISA, while urine sediment was used for cytology and detection of mutant p53 by PCR-SSCP followed by DNA sequencing. The sensitivity and specificity were 59% and 91.4% for VUC, 82% and 84.3% for fibronectin, and 37% and 100% for mutant p53; combination of the three parameters increased sensitivity to 95% but specificity was only 78.6%. A significant association was observed between disease recurrence and mutant p53, stage and lymph node involvement. Our results indicate that fibronectin had the highest sensitivity compared to VUC and mutant p53 in bladder cancer detection; however, mutant p53 had superior specificity compared to VUC and fibronectin. Mutant p53 is associated with disease recurrence and hence it has a significant prognostic role in bladder cancer.     

The Performance of the Xpert Bladder Cancer Monitor Test and Voided Urinary Cytology in the Follow-up of Urinary Bladder Tumors

BackgroundCystoscopy in complement with urinary cytology represents the gold standard for the follow-up of patients with urinary bladder tumours. Xpert Bladder Cancer Monitor Test (XBC) is a novel mRNA-based urine test for bladder cancer surveillance. The aim of the study was to evaluate the performance of the XBC and voided urinary cytology (VUC) in the follow-up of bladder tumours.Patients and methodsThe XBC was performed on stabilized voided urine and VUC was performed on urine samples. The results were compared to cystoscopic findings and histopathological results after transurethral resection of the bladder lesion.ResultsFor the prediction of malignant histopathological result sensitivity, the specificity and negative predictive value were 76.9%, 9 7.5% and 93.0% for the XBC and 38.4%, 9 7.5% and 83.3%, respectively for VUC. For the prediction of suspicious or positive cystoscopic finding sensitivity, the specificity and negative predictive value were 75.0%, 95.2%, and 93.0% respectively for the XBC and 41.7%, 97.6%, and 85.4% for VUC. The sensitivities for papilary urothelial neoplasms of low malignant potential (PUNLMP), low- and high-grade tumours were 0.0%, 66.7% an d 100.0% for the XBC and 0.0%, 66 .7% and 42.9%, respectively for VUC.ConclusionsThe XBC showed significantly higher overall sensitivity and negative predictive value than VUC and could be used to increase the recommended follow-up cystoscopy time intervals. Complementing the XBC and voided urinary cytology does not improve performance in comparison to the XBC alone.Key words: cystoscopy, Xpert BC Monitor Test, urinary bladder neoplasm, voided urinary cytology     

联合检测UBC、HA和CK20诊断膀胱癌的临床价值

背景与目的:膀胱癌是最常见的泌尿系统肿瘤,尿脱落细胞学检查是无创性诊断的金标准,但敏感性较低.本研究探讨联合运用尿膀胱癌抗原(urinary bladder cancer,UBC)、透明质酸(hyaluronic acid,HA)和细胞角蛋白20(cytokeratin 20,CK20)诊断膀胱癌的临床价值.方法:对64例膀胱癌患者、20例泌尿系良性疾病患者,在膀胱镜检查之前留尿,分别采用酶链免疫吸附实验、放射免疫分析和逆转录聚合酶链反应检测UBC、HA和CK20在尿液中的表达,同时行脱落细胞学检查,分析比较4种方法诊断膀胱癌的临床价值.结果:UBC、HA和CK20诊断膀胱癌的敏感性分别为85.9%(55/64)、89.1%(57/64)、78.1%(50/64),与脱落细胞学(40.6%)检查比较,差异有统计学意义(P<0.01);4种方法诊断膀胱癌的特异性分别为85,0%(17/20)、80.0%(16/20)、80%(16/20)和95%(19/20).各分级和分期肿瘤UBC、HA和CK20的敏感性分别高于尿脱落细胞学检查,UBC值各分级和分期比较差异无统计学意义(P>0.05).HA检测G2、G3组较G1组明显增高(P<0.01),但G2、G3组间比较差异无统计学意义(P>0.05);各分期之间比较差异无统计学意义(P>0.05).CK20检测随肿瘤的分级与分期的增高,敏感性增高(P<0.01).联合运用UBC、HA和CK20敏感性可达96.9%,特异性达100%.结论:联合UBC、HA和CK20能提高诊断膀胱癌的敏感性和特异性,初步诊断能够代替膀胱镜检查.     

Diagnostic performance of the urinary bladder carcinoma antigen ELISA test and multiparametric DNA/cytokeratin flow cytometry in urine voided samples from patients with bladder carcinoma.

BACKGROUND: The objective of the current study was to comparatively analyze the sensitivity and specificity of flow cytometric DNA/cytokeratin 8/18 measurements and the urinary bladder carcinoma antigen (UBC) enzyme linked immunoabsorbent assay (ELISA) test for the detection of bladder carcinoma in voided urine samples. METHODS: Eighty-one fresh urine voided samples, preserved frozen for a maximum period of 3 months, belonging to patients with an active bladder carcinoma (n = 37), patients who were free of disease as confirmed by cystoscopy (n = 19), patients receiving intravesical therapy (n = 17), and individuals with other benign and malignant conditions (n = 8), were collected. Flow cytometry measurements of thawed samples were based on the detection of cytokeratin (CK) 8+ and CK18+ cells using the 3F3 and 6D7 monoclonal antibodies alone or in combination with the measurement of cell DNA contents, after propidium iodide staining. Urinary bladder carcinoma antigen test was measured by ELISA. RESULTS: Patients were grouped according to the presence (n = 44) or absence (n = 29) of bladder carcinoma as confirmed by cystoscopy, and taking cutoffs of 9.7 microg/L for UBC-ELISA, 75% for the percentage of 3F3 (+) and 6D7 (+) cells, and 10.6% for the proportion of hyperdiplod cells that suggested a specificity of 83%, the individual sensitivity obtained for each parameter was 77%, 5%, 9%, and 77%, respectively. The presence of DNA aneuploid populations showed a relatively low sensitivity (36%) although it was the most specific parameter (93%). Combining UBC antigen test with the proportion of cells showing DNA content higher than 2n increased to 89% the sensitivity of the UBC antigen alone. However, false-positive results for both techniques were found in individuals with urologic diseases other than bladder carcinoma and in patients receiving intravesical therapy. CONCLUSIONS: The authors' results suggest that the combined use of the UBC antigen test and DNA/cytokeratin flow cytometry double stainings for the analysis of freshly obtained urine voided samples, cryopreserved to assure cellular integrity, is of great clinical utility for the detection of tumor recurrence in patients with bladder carcinoma.     

BTA检测在膀胱癌诊断中的价值

目的BTA检测与尿脱落细胞学检查结果比较,以明确在膀胶癌诊断中的应用价值.方法 收集1996年12月～1997年1月经膀胱镜及病理学检查确诊为膀胱乳头状移行细胞癌的病人共47例.每一例于膀胱镜检查前连续留取三次晨尿,行尿脱落细胞学检查.最后一次标本同时行BTA检测及尿液常规化验.结果BTA检测膀胱癌的敏感度为70.2%(33/47),尿脱落细胞学检查敏感度为25.5%(12/47),两者有非常显著性差异(P<0.001).共有8例(17.0%)患者两种检查结果均为阳性,10例(21.3%)患者两种检测结果均为阴性.另外,BTA检测对T1期膀胱癌患者的敏感度明显高于尿脱落细胞学检查,其结果分别为76.0%(19/25)和12.0%(3/25),统计学分析示有非常显著性差异(P<0.01).结论 BTA检测是一种有价值的膀胱癌诊断辅助措施,且使用方便,检测迅速,无创伤性,便于临床开展.