膀胱癌患者尿NMP22测定的临床意义

目的：评价尿核基质蛋白22（NMP22）在膀胱癌诊断和预后判定中的应用价值。方法：采用ELISA法测定18例膀胱癌和20例泌尿系良性疾病患者尿液中NMP22值,及10例膀胱移行细胞癌患者术后尿NMP22值。结果：18例膀胱癌患者尿NMP22的中位值为44．3IU／L,20例泌尿系良性疾病患者尿NMP22的中位值为5．8IU／L,二者相比判别有显著性意义（P＜0．02）。以10IU／L为临界值,诊断膀胱癌的敏感性为83％,特异性为70％,阴性预测值为82％。10例膀胱移行细胞癌患者术后尿NMP22中位值为7．8IU／L,与术前相比明显下降（P＜0．01）。尿NMP22在肿瘤分级间的差别无显著性意义。结论：尿NMP22作为一种灵敏、简便的早期诊断膀胱癌的瘤标,对于预后判断可能具有应用价值。     

膀胱癌患者尿NMP22与尿脱落细胞学检测的临床价值

目的研究核基质蛋白22（NMP22）与尿脱落细胞学在膀胱癌早期诊断、监测复发及判断预后中的临床价值。方法收集96份尿液标本,其中包括45例膀胱癌术前患者（经术后病理证实）,20例膀胱癌术后复测患者及3l例良性泌尿系疾病患者。均通过酶联免疫吸附法（ELISA）检测NMP22值,将其结果与尿脱落细胞学通过,检验的形式进行对比。结果45例膀胱癌术前患者NMP22的含量为9．3—112．5U／mL,中位数为48．7U／mL;31例良性泌尿系患者NMP22的含量为2．1～14．7U／mL,中位数为7．9U／mL;20例膀胱癌术后患者NMP22的含量为4．3～18．7U／mL,中位数为8．9U／mL,膀胱癌术前患者NMP22中位数明显高于良性泌尿系患者NMP22中位数,差异有显著统计学意义（P〈0．05）。以NMP22≥10U／mL为临界值,NMP22诊断膀胱癌的敏感性为82．2％,特异性为70．9％;尿细胞学的敏感性为31．1％。特异性为100％。20例膀胱癌术后患者经膀胱镜证实复发有9例。结论NMP22可以作为膀胱癌的早期筛查和术后随访的有效标志物。     

NMP 22与流式细胞术在膀胱癌诊断中的价值

目的：分析比较检测尿核基质蛋白22（NMP22）、流式细胞术（FCM）、 尿脱落细胞学检查3种无创方法诊断膀胱移行细胞癌（BTCC）的临床价值。方法：将85例同期住院病人分成BTCC组、泌尿系良性疾病组、泌尿系非尿路上皮恶性肿瘤组,分别应用酶联免疫吸附试验（ELISA）、FCM测定各组病人自排尿中NMP22和DNA含量,并同时行尿脱落细胞学检查。结论：BTCC组、泌尿系良性疾病组、泌尿系非路上皮恶性肿瘤组尿NMP22含量的中位数分别为16．1U／ml、7．2U／ml、4．5U／ml。BTCC组尿NMP22的含量与其他两组含量差别具有显著性意义（P＜0．05）。NMP22、FCM、尿脱落细胞诊断BTCC的敏感性分别为61．1％、69．4％、18．3％,特异性分别为67．4％、59．2％、100％。结论：尿NMP22测定,FCMDNA分析术检测BTCC具有比脱落细胞学更高的敏感性,可作为BTCC的辅助诊断手段。     

NMP22诊断膀胱移行细胞癌价值的评价

目的 :探讨核基质蛋白 2 2 (NMP2 2 )对膀胱移行细胞癌的临床诊断价值。方法 :选取 5 8例膀胱移行细胞癌患者为实验组 ,2 0例泌尿系统非尿路上皮肿瘤疾病的患者为对照组 1,10名健康志愿者为对照组 2 ,应用酶联免疫法测定三组受试者尿NMP2 2的含量。结果 :实验组尿NMP2 2中位含量为 2 3 .2× 10 3U/L ,明显高于对照组 1的 8.3× 10 3U/L和对照组 2的 2 .6× 10 3U/L (P <0 .0 1) ;尿NMP2 2检测膀胱移行细胞癌的敏感性为79% ,高于尿细胞学的 3 8% (P <0 .0 5 ) ;NMP2 2的阳性率与膀胱移行细胞癌的分期、分级以及肿瘤的形状、大小和数目无显著相关性。结论 :尿NMP2 2对膀胱癌的诊断有较高的敏感性 ,简便、无创 ,检测结果不受肿瘤的分化程度、生长方式、肿瘤大小和数目的影响     

核基质蛋白22检测与尿脱落细胞学检查在膀胱癌诊断中的价值

目的　探讨尿核基质蛋白 2 2 (NMP 2 2 )检测和尿脱落细胞学检查在膀胱移行细胞癌诊断中的价值。　方法　对 15 5例怀疑膀胱癌者进行尿NMP 2 2与尿细胞学检查 ,其中 95例经组织学证实为膀胱移行细胞癌。比较两者诊断膀胱癌的敏感性和特异性。　结果　尿NMP 2 2的敏感性为6 5 .3%、特异性为 70 .0 % ;尿细胞学的敏感性为 4 3.2 %、特异性为 83.3%。NMP 2 2在膀胱癌不同分级和分期中的敏感性优于尿细胞学 (P <0 .0 5 )。　结论　尿NMP 2 2检测在早期诊断膀胱癌方面优于尿细胞学检查 ,可以作为膀胱癌的早期检测指标。     

尿核基质蛋白检测在膀胱癌诊断中的应用价值评定

目的:研究尿核基质蛋白(NMP22)在膀胱癌临床诊断和预后判定中的应用价值。方法:采用双单抗夹心酶联免疫法(ELISA)检测84例膀胱肿瘤怀疑患者和20例正常健康志愿者尿液中NMP22的含量,同时行尿脱落细胞学检测。结果: 84例中,病理检查证实膀胱肿瘤56例, 良性泌尿系疾病28例。膀胱癌患者尿中NMP22水平(53. 0×103U/L)明显高于良性泌尿系疾病(8. 8×103U/L)和正常人群(7. 7×103U/L), NMP22水平与膀胱癌浸润深度和分化程度呈正相关;以104U/L为阳性临界值,NMP22诊断膀胱肿瘤的敏感性要明显高于尿脱落细胞学检查。结论:NMP22是膀胱癌患者尿中的良好瘤标,与膀胱癌侵袭能力和恶性程度密切相关,可以作为膀胱癌诊断和预后评估的指标。     

尿端粒酶、NMP22和ImmunoCyt联合检测在膀胱癌诊断中的应用

目的评价尿端粒酶、核基质蛋白22（NMP22）和ImmunoCyt测定在膀胱癌（BTCC）早期诊断中的应用价值,寻找早期诊断膀胱癌的有效方法。方法选择60例经病理诊断明确为早期膀胱移行细胞癌和60例非膀胱肿瘤患者,分别进行尿端粒酶、ImmunoCyt、NMP22和标准尿脱落细胞学检测。结果尿端粒酶、NMP22和ImmunoCyt和尿脱落细胞学的敏感度分别为58.3%、60.0%、61.6%、26.6%;准确度分别为75.8%,78.3%,78.3%和63.3%;特异度分别为93.3%,96.6%,95.0%和100%。三者联合检测与尿端粒酶、NMP22和ImmunoCyt单独检测相比,敏感度（分别为χ2=6.53,P〈0.05;χ2=5.17,P〈0.05;χ2=4.54,P〈0.05）和准确度（分别为χ2=4.01,P〈0.05,χ2=4.38,P〈0.05,χ2=4.91,P〈0.05）都有所提高;尿端粒酶、NMP22和ImmunoCyt联合检测的敏感度（χ2=28.06,P〈0.01）和准确度（χ2=16.2,P〈0.01）均高于尿脱落细胞学,差异有统计学意义。结论尿端粒酶、NMP22和ImmunoCyt是早期诊断膀胱移行细胞癌的一种高特异性指标,三者联合检测能提高膀胱癌的早期诊断率。     

尿及癌组织中Survivin的表达对膀胱癌的早期诊断价值

目的 通过对膀胱移行上皮癌患者尿脱落细胞及癌组织中抑制凋亡相关基因Survivin的检测，探讨早期发现、常规筛选膀胱癌且无损伤的方法。方法留取53例膀胱移行上皮癌、20例泌尿系其他疾病患者及10例健康志愿者新鲜中段晨尿200mL，对53例膀胱移行上皮癌患者术后癌组织，用巢式逆转录聚合酶链反应（nestedRT-PCR）检测Survivin的表达，同时行尿脱落细胞学检查及膀胱镜取材病检。结果用巢式RT—PCR检测53例膀胱移行上皮癌患者尿及癌组织中Survivin均有表达，所有样本尿中Survivin的表达敏感性为100％，特异性为90％。尿脱落细胞学敏感性为37．7％，特异性为100％。膀胱镜病检敏感性、特异性均为100％。尿及癌组织中Survivin与尿脱落细胞学敏感性比较有显著差异（P〈0．05），与膀胱镜检相同。而特异性分别为90％、100％、100％，P〉0．05，无差异。结论用巢式RT-PCR方法检测膀胱移行上皮癌患者尿及癌组织中Survivin的表达，其敏感性、特异性相同。尿脱落细胞Survivin表达敏感性、特异性高。尿取材无损伤、方便，敏感性优于尿脱落细胞学检查，与膀胱镜检相当，特异性与尿脱落细胞学检查及膀胱镜病检无差别，且对膀胱癌前病变的归转有一定价值。检测尿中Survivin有望成为临床诊断、筛检膀胱癌的较可靠方法。     

核基质蛋白22在膀胱移行上皮癌诊断中的价值(附48例报告)

目的:评价患者尿中核基质蛋白22(NMP 22)在泌尿系上皮肿瘤诊断中的意义。方法:采用ELISA法测定48例膀胱移行上皮肿瘤患者尿中NMP 22的值,并与尿脱落细胞学检查进行比较。结果:48例膀胱移行上皮肿瘤患者尿NMP 22的中位值为19.53 IU/L。以10 IU/L为临界值,NMP 22诊断膀胱移行上皮肿瘤的敏感性为86.96％,特异性为50％;尿脱落细胞学检查的敏感性为17.39％,特异性为100％。尿NMP 22在肿瘤的分期、分级间的差别无显著性意义(P>0.05)。结论:尿NMP 22检测比尿脱落细胞学检查更敏感,可以作为血尿患者和既往膀胱肿瘤患者的首选筛选方法。     

膀胱移行上皮癌患者尿及癌组织中Survivin表达的临床意义

目的：探讨Survivin对膀胱癌早期发现、常规筛选且无损伤的方法,研究其与肿瘤病理分级（期）的相关性。方法：留取53例膀胱移行上皮癌、20例泌尿系其他疾病、10例健康志愿者新鲜中段晨尿,同上53例术后癌组织。利用巢式RT—PCR、实时定量PCR技术检测Survivin的表达,同时行尿脱落细胞学及膀胱镜病检。结果：53例膀胱癌患者尿及癌组织中Survivin均有表达,敏感性为100％,特异性为90％。与尿脱落细胞学敏感性比较两者差异有统计学意义（P〈0．05）,与膀胱镜检比较差异无统计学意义。三种方法特异性比较差异无统计学意义（P〉0．05）。癌组织中Survivin的量与肿瘤病理分级（期）正相关（P〈0．01）。结论：检测尿脱落细胞中Survivin的表达有望成为临床诊断、筛检膀胱癌的较可靠方法。Survivin在膀胱的演进过程中可能起重要作用,可望作为检测膀胱癌恶化进展的指标。     

Comparison of the nuclear matrix protein 22 with voided urine cytology and BTA stat test in the diagnosis of transitional cell carcinoma of the bladder.

OBJECTIVE: To assess sensitivity, specificity, accuracy, positive predictive value and negative predictive value of nuclear matrix protein 22 (NMP22) test, BTA stat test and cytology in the urine of patients with a spectrum of urologic conditions, including bladder cancer. METHODS: A total of 140 patients (40 with bladder cancer) provided a urine sample which was divided into appropriate aliquots for each of the tests cited above. The endoscopist, pathologist, cytologist and the person performing BTA stat test and NMP22 test were blinded as to the results of the other tests. RESULTS: Receiver-operating characteristics curve interpretation determined that 12.0 U/ml was an optimal reference value for NMP22 to detect transitional cell carcinoma of the bladder in this patient group. Comparative results demonstrate a clear superiority of NMP22 and BTA stat tests in sensitivity in bladder cancer detection (p < 0.01), while cytology and NMP22 were better than BTA stat test in specificity (p < 0.05). CONCLUSIONS: NMP22 and BTA stat test results represented significant improvement over urinary cytology for detection of transitional cell carcinoma. The sensitivities of NMP22 and BTA stat tests for detection of transitional cell carcinoma in this group of patients were as much as twice that of cytology. When the cutoff value of urinary NMP22 was set at 12.0 U/ml, NMP22 was more accurate than the other tests (p < 0.05).     

Risk stratification for bladder tumor recurrence, stage and grade by urinary nuclear matrix protein 22 and cytology

PURPOSE: To test the hypothesis that voided urinary levels of nuclear matrix protein 22 (NMP22) would add to the predictive ability of urine cytology in the diagnosis, staging and grading of bladder transitional cell carcinoma (TCC), and to evaluate the diagnostic performance of different NMP22 cut-points. MATERIALS: NMP22 level and barbotage cytology were evaluated in voided urine specimens collected before cystoscopy from 302 subjects with a history of TCC, 32 subjects with benign urologic pathologies, and 10 healthy volunteers. RESULTS: 180 patients (52%) had bladder TCC. Higher levels of NMP22 and positive cytology were independently associated with an increased risk of TCC, invasive stage, and high grade. The NMP22 value with equal sensitivity and specificity for prediction of bladder cancer was 6.5U/ml; for prediction of grade 3 TCC it was 13.5U/ml; and for prediction of invasive tumor stage it was 17.4U/ml. The NMP22 cut-point of 6.5U/ml outperformed the 10U/ml cut-point in all pathologic stages and grades. The diagnostic sensitivity of the cytology and NMP22 combined was superior across all pathologic stages and grades to that of either marker alone. NMP22 and cytology stratified patients into groups with significantly different risk for TCC presence, invasive stage, and high grade. CONCLUSIONS: 6.5U/ml is a robust NMP22 cut-point for bladder cancer surveillance. The diagnostic sensitivities of the combined NMP22 and cytology for TCC presence, stage, and grade were significantly higher than those of single marker alone. The combination of urine cytology and NMP22 could be used to tailor the frequency of cystoscopic follow up.     

Urinary cytology and nuclear matrix protein 22 in the detection of bladder cancer recurrence other than transitional cell carcinoma

OBJECTIVE

To assess the value of nuclear matrix protein‐22 (NMP22), compared with urinary cytology, in predicting the recurrence of bladder cancer that is not transitional cell carcinoma (non‐TCC).

PATIENTS AND METHODS

We tested the sensitivity, specificity and the predictive accuracy of NMP22 in the context of non‐TCC bladder cancer recurrence, and compared it to the performance of urinary cytology. The study group comprised 2687 patients with history of non‐muscle‐invasive bladder cancer from 10 centres across four continents.

RESULTS

The mean patient age was 64.8 years and 75.4% were men; of all patients, 513 (19.1%) had positive urinary cytology, 906 (33.7%) had a positive NMP22 test (≥10 units/mL) and 80 (3.0%) had non‐TCC recurrence. Most of these, i.e. 60 (75%), were stage ≥T2. The sensitivity and specificity of urinary cytology were, respectively, 20.0% and 94.8%, vs 77.5% and 81.8% for NMP22 of ≥10 units/mL. The predictive accuracy of urinary cytology was 57.5%, vs 87.1% for NMP22 ≥ 10 units/mL. A combined model that included dichotomized NMP22 and urinary cytology was 85.3% accurate.

CONCLUSION

The ability of a NMP22 level of ≥10 units/mL to predict non‐TCC recurrence was better than that of urinary cytology, suggesting that NMP22 might have a role in the surveillance of patients at risk of non‐TCC recurrence.     

BTA quantitative assay and NMP22 testing compared with urine cytology in the detection of transitional cell carcinoma of the bladder

PURPOSE: Both BTA TRAK and NMP22 urine concentrations have shown a sensitivity superior to urine cytology in the detection of bladder cancer. We compared these tumor markers with urine cytology performed on 3 consecutive samples and evaluated by an expert cytopathologist. PATIENTS AND METHODS: The investigations were conducted on 94 patients undergoing a diagnostic cystoscopy for a high suspicion of bladder cancer (group 1) and on 102 patients with previous history of transitional cell carcinoma awaiting a follow-up cystoscopy (group 2). Biopsy specimens were obtained also from tumor negative patients. Immunoassays for BTA TRAK and NMP22 were carried out according to standard methods. The choice of the cut-off was based on the ground of sensitivity and specificity curves intersection. Urine cytology results were expressed as positive, negative and 'dubious'. RESULTS: Overall sensitivity was 56% for NMP22 (cut-off 11 U/ml) and 57% for BTA TRAK (cut-off 60 U/ml). When dubious results were considered as positive cases, urine cytology achieved a sensitivity of 73.3%. Assuming dubious cases as negative results, urine cytology sensitivity resulted 59.3%. When the 2 groups of patients were evaluated separately with different cut-off, there was no significant gain in sensitivity for BTA TRAK and NMP22 over urine cytology. CONCLUSIONS: Urine cytology performed on 3 samples showed the highest sensitivity and specificity. The diagnostic advantage of urine cytology over BTA TRAK and NMP22 was maintained when patients were stratified by tumor grade.     

Comparison of the nuclear matrix protein 22 with voided urine cytology in the diagnosis of transitional cell carcinoma of the bladder

Several urinary markers for transitional cell carcinoma have been investigated, including urine cytology, bladder tumor antigen, autocrine motility factor receptor and fibrin degradation products. Unfortunately, they have poor overall sensitivity. The United States Food and Drug Administration have recently approved nuclear matrix protein (NMP 22) for the detection of occult or rapidly recurring disease after transurethral resection of bladder tumor. The objective of the current study was to assess the sensitivity of NMP 22 for the detection of bladder carcinoma, as well as to correlate the NMP 22 values with multiplicity of tumor, tumor size, configuration, stage and grade respectively. A total of 78 patients (38 with bladder cancer) provided a urine sample which was divided into appropriate aliquots for each of urine cytology and NMP 22. Comparative results demonstrate a clear superiority of NMP 22 in bladder cancer detection (52.6% vs 31.6% sensitivity), while specificity was in favor of urine cytology (100% vs 82.5%). For superficial tumors, sensitivity was 78.5% for NMP 22 and 41.6% for cytology and for invasive cancers, sensitivity was 90% for NMP 22 and 60% for cytology. Urinary NMP 22 levels were significantly correlated with tumor grade and were significantly higher in large tumors than small tumors. NMP 22 test results showed sufficient sensitivity in comparison with urine cytology for the detection of transitional cell carcinoma. However, we do not think that it is a useful tool as a substitute for endoscopic examination for the detection and surveillance in bladder cancer.     

Clinical application of NMP22 and urinary cytology in patients with hematuria or a history of urothelial carcinoma

For evaluation of the clinical application of immunoassay for nuclear matrix protein 22 (NMP22 immunoassay) and urinary cytology for early diagnosis and detection of bladder cancer in patients with hematuria and/or a previous history of bladder cancer, 209 urine samples obtained from 137 patients presenting episodes of hematuria or a history of bladder cancer were assayed for NMP22 levels and/or prepared for cytology examination. Biopsy was performed when any visible tumor was identified during cystoscopy examination. The median NMP22 concentrations measured in samples taken from patients with active bladder cancer, from patients with a history of bladder cancer but no active disease, from patients with hematuria, and from healthy volunteers were 18.95, 5.45, 6.39, and 3.75 U/ml, respectively. The urinary NMP22 level recorded for patients with urothelial carcinoma was significantly higher than that noted for individuals without active disease. The sensitivity of the NMP22 assay and of urinary cytology in diagnosing bladder cancer was 69% and 67%, respectively. In contrast, the specificity of these two diagnostic modalities reached 72% and 93%, respectively. The NMP22 assay is slightly more sensitive but less specific than urinary cytology in detecting bladder cancer. This study indicates that determination of urinary NMP22 levels is a useful and noninvasive tool for the detection of bladder cancer because of its high sensitivity. The urinary NMP22 assay may be used as a first-line routine screening method; however, it cannot replace the use of urinary cytology because of its lower specificity.     

NMP22与BTA stat检测在膀胱肿瘤诊断中的应用

目的评价NMP22和BTAstat诊断膀胱肿瘤的价值.方法对82例临床怀疑膀胱肿瘤的患者,在膀胱镜检查前将尿样分为3份,分别进行NMP22、BTAstat和脱落细胞学检测,分析比较3种方法的敏感性、特异性和阳性预测价值.结果82例中病理证实膀胱肿瘤32例,其他疾病50例.NMP22诊断膀胱肿瘤敏感性为87.5%,与BTAstat(65.6%)、细胞学(21.9%)比较,差别有显著性意义(P<0.05).3种方法诊断特异性分别为84.0%、64.0%和100.0%.阳性预测值分别为77.8%、53.9%和100.0%.结论NMP22是一种简单、敏感、非侵袭性的早期诊断膀胱肿瘤的肿瘤标记物.     

影响尿核基质蛋白诊断膀胱癌的干扰因素

目的：探讨尿核基质蛋白(NMP22)在膀胱癌诊断中的特异性和阳性预测值价值。方法：对196例临床怀疑膀胱癌的患者，在膀胱镜检查前留取新鲜自排尿．每个尿标本均行尿细胞学、尿常规、尿培养和NMP22检测。所有患者均行膀胱镜检查。结果：196例中，病理检查证实膀胱癌41例，其他疾病155例。41例膀胱癌患者中，检测出NMP22 33例(80．5%)，而尿细胞学检测阳性仅为11例(26．8％)。在67例NMP22异常者中，除33例诊断为膀胱癌外，假阳性为34例，故特异性和阳性预测值分别为78．1％和49．3％。假阳性结果主要出现在泌尿系感染或炎症、泌尿系结石、泌尿系异物、肠道代膀胱、其他泌尿生殖系肿瘤和器械操作6种情况．排除这6种干扰因素后，NMP22检测的特异性和阳性预测值分别升高至96．2％和91．7％。结论：排除干扰因素能明显改善NMP22诊断膀胱癌的特异性和阳性预测值，提高其临床应用价值。