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。     

CD15在膀胱癌尿脱落细胞学检测中的应用价值

目的：探讨CD15在膀胱癌尿脱落细胞学诊断中的应用价值。方法：采用EnVision免疫细胞学染色方法，检测52例膀胱尿路上皮癌和16例非肿瘤病人尿脱落细胞标本中CD15的表达情况，并与细胞病理学检测相比较。结果：以5％尿脱落上皮细胞CD15染色阳性为膀胱癌诊断阈值，其敏感性和特异性分别为84．6％和87．5％，敏感性显著高于细胞学检查。结论：尿脱落细胞CD15免疫染色，有助于膀胱尿路上皮癌的诊断。     

膀胱移行上皮癌尿脱落细胞端粒酶活性检测

[目的]检测尿脱落细胞端粒酶活性表达对膀胱移行上皮癌的诊断价值.[方法]应用PCR为基础的端粒重复片段扩增方法(TRAP-Hyb Kit)分别检测52例膀胱移行上皮癌患者及10例泌尿生殖系良性疾病患者尿脱落细胞端粒酶活性表达情况,并与尿脱落细胞学检查结果进行比较.[结果]52例膀胱移行上皮癌患者中有34例的自排尿标本中可检测出端粒酶活性表达(65.4%);尿脱落细胞学检查阳性例数为11例(11/30,36.7%);两者比较差异有显著性(P＜0.05).泌尿生殖系良性疾病的尿脱落细胞端粒酶的阳性率为10.0%.但端粒酶活性与肿瘤的分级无相关性.[结论]尿脱落细胞端粒酶活性检测作为无创性的检测方法,可作为膀胱移行上皮癌早期诊断、术后监测的一种有效手段.     

尿液中核基质蛋白22联合端粒酶活性检测诊断膀胱癌的实验研究

目的:探讨尿液中核基质蛋白22(NMP22)联合端粒酶活性检测在膀胱癌诊断中的价值,寻找一种敏感特异的无创性方法诊断膀胱癌.方法:收集60例膀胱癌和40例非膀胱癌患者新鲜尿液,用化学发光分析法检测尿液中NMP22水平,TRAP-PCR-ELISA法检测尿脱落细胞端粒酶活性,并同时行尿脱落细胞学检查,对比三者对膀胱癌诊断的敏感性和特异性.结果:尿液中NMP22对膀胱癌诊断的敏感性83.3％,特异性43.3％;端粒酶敏感性82％,特异性90％;细胞学检查敏感性30％,特异性100％.NMP22联合端粒酶活性检测,敏感性96％,特异性78％.结论:联合检测NMP22、端粒酶活性有较高的敏感性和特异性,具有一定临床诊断、随访价值.     

尿脱落细胞LewisX检测诊断膀胱尿路上皮癌的价值

目的：探讨LewisX抗原在膀胱尿路上皮癌非侵袭性诊断中的应用价值。方法：采用EnVision免疫细胞化学方法，检测52例膀胱尿路上皮癌和16例非肿瘤患者尿脱落细胞标本中LewisX抗原的表达情况，并与细胞病理学检测结果相比较。结果：尿路上皮癌诊断的敏感性和特异性分别为84．6％和87．5％，其敏感性显著高于细胞病理学。结论：尿脱落细胞LewisX抗原免疫染色，是检测膀胱尿路上皮癌可行的较敏感的非侵袭性方法。     

尿核基质蛋白22和细胞角蛋白18在膀胱移行细胞癌中的表达及其临床意义

目的 探讨尿核基质蛋白22(NMP22)和细胞角蛋白18(CK18)在膀胱移行细胞癌中的表达及其临床意义.方法 采用酶联免疫吸附法(ELISA)对293例膀胱移行细胞癌、400例非移行细胞肿瘤、105例泌尿系良性病患者进行尿NMP22和CK18蛋白水平的检测.结果 膀胱移行细胞癌患者术前NMP22和CK18表达中位值分别为17.3 U/ml和484.2 U/L,非移行细胞肿瘤患者分别为6.8 U/ml和156.0 U/L,良性疾病患者分别为2.3 U/ml和66.6 U/L,3组之间进行比较,差异有统计学意义(P<0.001).以NMP22 10 U/ml和CK18 120 U/L为界值,其对膀胱移行细胞癌诊断的敏感度分别为79.2%和78.2%,特异度分别为88.6%和82.9%,两者联合检测的敏感度为91.7%.对术后患者动态观察,治疗有效患者的NMP22和CK18表达水平较治疗前明显下降,而复发、转移的患者则上升,差异有统计学意义(P<0.01).NMP22和CK18对膀胱移行细胞癌的检测有显著的相关性(r=0.689 P<0.0001).NMP22和CK18表达水平在不同病理分级和不同分期的患者中比较,差异有统计学意义(均P<0.01).结论 尿NMP22和CK18检测可作为膀胱移行细胞癌术前诊断、病情监测重要指标,两者联合检测可进一步提高敏感度.     

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。     

尿细胞角蛋白检测与尿脱落细胞学检查在膀胱癌诊断中的价值

目的:探讨尿细胞角蛋白检测与尿脱落细胞学检查在膀胱移行细胞癌诊断中的价值。方法:136例怀疑膀胱癌者,进行尿细胞角蛋白8和18的含量(UBC值)。检测与尿细胞学检查,其中87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:尿细胞角蛋白的敏感性为70.1%,特异性为73.3%;尿细胞学的敏感性为42.5%,特异性为83.7%。尿细胞角蛋白在膀胱癌不同分级和分期中的敏感性优于尿细胞学(P<0.05)。结论:尿细胞角蛋白的检测在早期诊断膀胱癌方面优于尿细胞学检查,可作为膀胱癌的早期检测指标。     

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.     

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。     

NMP22肿瘤标志物诊断尿路上皮癌的初步评价

目的：探讨基质蛋白（ＮＭＰ２２）对尿路上皮癌临床诊断的价值。方法：应用酶联免疫法检测２８例尿路上皮癌及４例非尿路上皮肿瘤术前尿液的ＮＭＰ２２的含量。结果：尿路上皮癌ＮＭＰ２２的阳性率为７１．４％，其与病理分级、分期无明显相关性，而尿细胞学阳性率为３２．１％，４例非尿路上皮癌患者尿ＮＭＰ２２含量检测结果的为阴性。结论：尿液ＮＭＰ２２含量的测定有助于尿路上皮癌的诊断，且快速方便。     

Clinical application of NMP22 in the management of transitional cell carcinoma of the bladder

The combination of a noninvasive, quantitative immunoassay, NMP22, with voided urinary cytology prior to cystoscopy was evaluated in patients with urothelial transitional cell carcinoma. Fifty-six patients with a history of transitional cell carcinoma were evaluated. Voided urine was obtained for NMP22 and cytology prior to cystoscopy. One hundred and twenty-three NMP22 assays, 124 cytologies, and 124 cystoscopies were performed. The type of anesthesia used for cystoscopic evaluation was determined by the NMP22 value in 30 patients. Cystoscopy results were considered positive on biopsy-confirmed malignancy. The reference value used for NMP22 was 10.0 U/ml. NMP22, cytology, and the combination of NMP22 and cytology were compared to cystoscopy and to pathologic grading and staging. Thirty-four recurrent transitional cell carcinoma episodes occurred; 22 were low-grade (I-II), and 12 were high-grade (III-IV). Twenty-seven were stage Ta; four were T1; and three were T3b or 4. Within this group, NMP22 detected low- and high-grade tumors equally, as compared to cytology, which was sensitive only to high-grade tumors. Nineteen patients were NMP22-negative and underwent cystoscopy under topical anesthesia; 17 were tumor-free. Eleven patients were NMP22-positive and had anesthesia, and all had visible lesions, which were subjected to biopsy and were resected. Six lesions were tumors, five were inflammatory. Overall sensitivity of combined NMP22 and cytology was 70%; specificity was 72%; positive predictive value was 54%; and negative predictive value was 77%. An accurate assessment of the risk of a bladder cancer can be obtained with NMP22, cytology, and cystoscopy in patients with a history of bladder cancer. NMP22 values can be used to determine the level of anesthesia for cystoscopy in patients with a history of bladder cancer.     

Urinary tumor marker for urothelial cancer]

The urinary tumor markers BTA, BFP and NMP22 used for urothelial cancer in Japan are reviewed briefly. We also evaluate and compare the sensitivity and specificity of BTA, BFP and NMP22 with urine cytology in detecting bladder cancer in 24 of our patients. The results showed that the sensitivity with urine cytology, BTA, BFP and NMP22 was 37, 54, 66 and 62% respectively. The specificity of BTA, BFP and NMP22 with urine cytology was 100, 65, 60 and 70% respectively. The sensitivity with BTA, BFP and NMP22 for urothelial cancer was higher than that with urine cytology. However, all except for urine cytology showed high false positive rates (83-90%) for urinary tract infection. These markers may thus complement urine cytology, which has a low sensitivity for urothelial cancer. Quite possibly they could act as low-cost and useful tumor markers, which could in turn reduce the number of invasive cystoscopic examinations. However, considering their high false positive rates for benign disease such as urinary tract infection, we must acknowledge that an ideal urothelial tumor marker, which is simple, non-invasive, inexpensive and accurate with high sensitivity and specificity has yet to be developed.     

RT-PCR法检测尿脱落细胞中XIAP的表达在膀胱癌诊断中的价值

目的：比较膀胱癌患者尿液脱落细胞中XIAP表达的RT-PCR检测法和常规尿脱落细胞病理学检测在膀胱癌诊断中的临床价值。方法：采用逆转录聚合酶链反应技术（RT-PCR）检测51例膀胱尿路上皮癌患者尿液脱落细胞中XIAP-mRNA的表达,同时行常规尿脱落细胞病理学检测,20例非肿瘤人员作为对照组。结果：实验组51例尿脱落细胞XIAP-mRNA RT-PCR检测阳性27例（53%）,尿脱落细胞学病理学检测阳性12例（24%）,对照组20例尿脱落细胞XIAP-mRNA检测阳性1例（5.0%）,对照组尿脱落细胞病理学检测阳性0例（0%）。实验组RT-PCR检测膀胱尿路上皮癌患者尿脱落细胞中XIAP表达的敏感性高于尿脱落细胞病理学检测,差异有极显著统计学意义（P〈0.01）,实验组RT-PCR检测膀胱尿路上皮癌患者尿中XIAP表达的敏感性显著高于非肿瘤对照组,差异有极显著统计学意义（P〈0.01）。结论：膀胱尿路上皮癌患者尿脱落细胞中XIAP表达的RT-PCR检测法较常规尿脱落细胞病理学检测更敏感,临床上作为膀胱癌的筛选方法,有一定的临床价值。     

尿肝细胞生长因子和核基质蛋白22含量与膀胱尿路上皮癌分期和分级的关系

 [摘要] 目的 探讨膀胱癌患者尿中肝细胞生长因子（HGF）和核基质蛋白22（NMP22）表达水平与膀胱癌分期和分级的关系。方法 膀胱移行细胞癌（TCC）接受保留膀胱手术的患者48例,其中19例灌注卡介苗（BCG）联合白介素2（IL-2）;29例灌注吡柔比星（THP）。采用酶联免疫吸附法（ELISA）分别检测灌注前、灌注后6月尿中HGF和NMP22的含量。结果 术后12个月复发率12.5%。灌注前尿HGF水平与肿瘤的分级、分期呈正相关（p＜0.05）,NMP22与肿瘤的分级呈正相关。HGF、NMP22和尿细胞学对膀胱癌术后复发的敏感性分别为100% ,83.3%和66.7%;特异性分别为62%, 57.1%和97.6%。结论 HGF和NMP22均为膀胱癌患者尿中良好肿瘤标志物,与肿瘤的分期和分级密切相关,结合尿细胞学检测可以作为膀胱癌早期筛查和诊断的有效指标。     

Comparison of NMP22 BladderChek test and urine cytology for the detection of recurrent bladder cancer

OBJECTIVE: To assess the clinical performance of the NMP22 BladderChek test, which is a qualitative test, and to compare it with voided urine cytology for the detection of recurrent bladder cancer. We also evaluated whether cystoscopy can be omitted from the surveillance protocol by combining the two tests. METHODS: A total of 131 patients with a history of superficial transitional cell carcinoma of the bladder provided urine samples before a cystoscopic examination. Urine samples were assayed for the presence of NMP22 using the NMP22 BladderChek test and cytology was performed by a cytopathologist. Selected patients underwent a biopsy, with appropriate additional therapy. Results of the two tests were compared with that the results of cystoscopy, which was retained as the gold standard. For positive biopsies, the results of the NMP22 test and cytology were also correlated with the tumor stage and grade. RESULTS: Of the 46 recurrences detected by cystoscopy, the NMP22 test was positive in 39 cases and cytology in 19 cases. The sensitivity of the NMP22 test was 85%, which was significantly greater than that of cytology (41%). In particular, for low-risk tumors it was eight times more sensitive than cytology. The specificities of the NMP22 test and cytology were 77 and 96%, respectively. Combining the two tests increased overall sensitivity to 91%. However, 9% of the tumors were still not detected. CONCLUSION: The NMP22 BladderChek test is an in vitro qualitative test that is easily available and cheap; it can be performed by a urologist in the office and results can be interpreted within 30 min. The NMP22 test is superior to cytology for all grades and stages in the detection of recurrence in patients with a history of superficial bladder cancer. Our study indicates that the NMP22 test can be used as a substitute for urine cytology. The NMP22 test cannot replace cystoscopy, but it can be used as an adjunct to cystoscopy in the surveillance protocol for patients with superficial bladder cancer.     

RT-PCR法检测尿脱落细胞中XIAP的表达在膀胱癌诊断中的价值

目的:比较膀胱癌患者尿液脱落细胞中XIAP表达的RT-PCR检测法和常规尿脱落细胞病理学检测在膀胱癌诊断中的临床价值。方法:采用逆转录聚合酶链反应技术(RT-PCR)检测51例膀胱尿路上皮癌患者尿液脱落细胞中XIAP-mRNA的表达,同时行常规尿脱落细胞病理学检测,20例非肿瘤人员作为对照组。结果:实验组51例尿脱落细胞XIAP-mRNA RT-PCR检测阳性27例(53%),尿脱落细胞学病理学检测阳性12例(24%),对照组20例尿脱落细胞XIAP-mRNA检测阳性1例(5.0%),对照组尿脱落细胞病理学检测阳性0例(0%)。实验组RT-PCR检测膀胱尿路上皮癌患者尿脱落细胞中XIAP表达的敏感性高于尿脱落细胞病理学检测,差异有极显著统计学意义(P<0.01),实验组RT-PCR检测膀胱尿路上皮癌患者尿中XIAP表达的敏感性显著高于非肿瘤对照组,差异有极显著统计学意义(P<0.01)。结论:膀胱尿路上皮癌患者尿脱落细胞中XIAP表达的RT-PCR检测法较常规尿脱落细胞病理学检测更敏感,临床上作为膀胱癌的筛选方法,有一定的临床价值。