荧光原位杂交(FISH)技术在尿路上皮癌诊断中的应用研究

目的探讨荧光原位杂交(fluorescence in situ hybridization,FISH)技术在尿路上皮肿瘤诊断中的价值。方法以89例血尿待查患者作为研究对象,分别进行尿脱落细胞学检查和FISH检测,并对其结果进行分析和对比。结果尿脱落细胞学检查和FISH检测对于诊断尿路上皮肿瘤的总敏感性分别为52.2%和89.6%(P<0.05),特异性分别为95.5%和90.9%(P=0.546),诊断符合率分别为62.9%和89.9%(P<0.05)。两种检测方法在尿路上皮肿瘤的诊断总敏感性和诊断符合率方面的差异均具有统计学意义;而在特异性方面的差异则无统计学意义。结论对于尿路上皮癌的检测,FISH检测的敏感性明显高于尿脱落细胞学检查,而两者特异性的差异不具统计学意义。FISH技术是一种尿路上皮癌早期诊断及术后监测的新方法。     

尿脱落细胞荧光原位杂交技术在尿路上皮癌诊断中的应用

目的:分析尿脱落细胞荧光原位杂交技术(FISH)在尿路上皮肿瘤诊断中的应用价值。方法:对205例临床疑诊尿路上皮肿瘤患者的尿脱落细胞进行FISH检测,并与组织病理学结果进行对照,总结FISH检测方法对尿路上皮癌诊断的敏感性与特异性。结果:153例尿路上皮癌、52例非尿路上皮癌患者在术前接受了尿脱落细胞FISH检测,术后均经病理检查确定诊断。FISH检测尿路上皮癌的敏感性为54.2%,特异性为94.2%。结论:尿脱落细胞FISH检测对于诊断尿路上皮癌具有高度的特异性。     

尿脱落细胞黏蛋白7 mRNA检测在膀胱癌诊断中的价值

目的 探讨尿脱落细胞黏蛋白7(Muc 7)mRNA检测在膀胱尿路上皮癌诊断中的价值.方法 采用RT-PCR方法检测52例膀胱癌患者和34例泌尿系非肿瘤患者尿脱落细胞中Muc7 mRNA表达情况,同时行尿细胞学检查,比较两种方法诊断膀胱癌的敏感性和特异性.膀胱癌患者52例,男30例,女22例.年龄41～87岁,平均65岁.TNM分期:Ta 1例、T1 22例、≥T2 29例.WHO分级:G1 18例、G2 14例、G3 20例.泌尿系非肿瘤患者34例,男23例,女11例.年龄30～75岁,平均58岁.结果 52例膀胱癌患者中Muc 7 mRNA检测阳性44例,敏感性为84.6%;34例非泌尿系肿瘤患者Muc 7 mRNA阴性29例、假阳性5例,特异性为85.2%,假阳性率为14.7%.膀胱癌患者尿脱落细胞检测阳性18例,敏感性为34.6%;非泌尿系肿瘤患者尿脱落细胞检测阴性31例、假阳性3例,特异性为91.2%,假阳性率为8.8%.尿Muc 7 mRNA检测诊断膀胱癌的敏感性优于尿脱落细胞学检查,差异有统计学意义(P<0.01);2种检测方法特异性及假阳性率比较,差异均无统计学意义(P>0.05).结论 尿Muc 7 mRNA检测诊断膀胱尿路上皮癌的敏感性优于尿脱落细胞学检查,可以作为膀胱癌的辅助检测指标.     

膀胱癌患者尿脱落细胞存活素表达的临床意义

目的　探讨膀胱移行细胞癌 (TCCB)患者尿脱落细胞存活素 (survivin)表达的临床意义。　方法　采用巢式RT PCR方法检测 5 6例TCCB、2 8例对照组 (其中 8例膀胱外泌尿系肿瘤患者、10例非肿瘤泌尿系疾病患者及 10例健康者 )尿脱落细胞存活素的表达。　结果　 5 6例TCCB患者中尿脱落细胞存活素阳性表达 5 1例 (91.1% ) ,T1表达率 90 .5 % (19/ 2 1) ,T2～ 491.4 % (32 / 35 ) ;G1表达率90 .6 % (2 9/ 32 ) ,G2 90 .9% (10 / 11) ,G3 92 .3% (12 / 13) ,存活素表达与临床分期和病理分级不相关 (P >均 0 .0 5 )。对照组 2 8例中仅 1例血尿患者存活素阳性表达 (3.6 % )。TCCB组与对照组存活素阳性率比较差异有显著性意义 (P <0 .0 1)。尿脱落细胞存活素表达诊断TCCB的敏感性为 91.1% ,特异性为96 .4 %。　结论　尿脱落细胞存活素检测诊断TCCB敏感性、特异性高 ,无创 ,可作为诊断TCCB的敏感指标。     

核基质蛋白22在上尿路移行细胞癌诊断中的作用

目的　探讨核基质蛋白 2 2 (NMP 2 2 )在上尿路移行细胞癌诊断中的作用。　方法　对2 4例肾盂癌及输尿管癌患者和 2 0例良性泌尿系疾病患者尿中NMP 2 2浓度及尿细胞学进行检测 ,计算诊断敏感性和特异性。　结果　 2 4例TCC患者尿液标本尿细胞学阳性 14例 ,NMP 2 2阳性 2 1例 ;2 0例良性泌尿系疾病患者尿液标本细胞学阳性 1例 ,NMP 2 2阳性 4例 ,NMP 2 2的诊断敏感性和特异性分别为 87.5 %和 80 .0 % ,尿细胞学为 5 8.3%和 95 .0 % ,比较二者敏感性差别有显著性意义。　结论　NMP 2 2可能成为检测上尿路移行细胞癌的良好辅助手段     

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。     

荧光原位杂交技术在膀胱尿路上皮癌诊断中的临床应用

目的 探讨荧光原位杂交(FISH)技术运用于膀胱尿路上皮癌的诊断价值.方法 收集20例健康志愿者的新鲜晨尿,运用荧光标记的3号、7号、17号染色体着丝粒探针及9号染色体p16位点探针,对尿液标本中的脱落细胞染色体进行FISH技术检测,建立正常人群的阈值.收集158例怀疑为膀胱尿路上皮癌患者的新鲜晨尿,在行膀胱镜检查前,同期进行FISH技术与尿脱落细胞学检测,运用统计学方法,比较FISH技术与尿脱落细胞学检测的敏感性与特异性.结果 FISH与尿脱落细胞学的敏感性分别为84.8%和43.8%,FISH敏感性高于尿脱落细胞(P<0.05),FISH与尿脱落细胞学特异性分别为89.1%和87.0%,两者无统计学差异(P>0.05),在不同的肿瘤病理分级中,FISH的敏感性都高于尿脱落细胞,并且FISH敏感性随肿瘤分级逐级升高(P<0.05).结论 FISH技术具有较高的敏感性和特异性,可以作为国人膀胱尿路上皮癌筛查、诊断的新方法.     

荧光原位杂交在膀胱尿路上皮癌诊断中的应用

目的评价尿脱落细胞荧光原位交(fluorescenceinsituhybridization,FISH)检测在膀胱肿瘤诊断中的应用价值。方法分别对69例疑似膀胱尿路上皮癌及20例对照组的尿液标本进行FISH及细胞学检测,比较两者诊断的敏感性及特异性,统计膀胱尿路上皮癌各个染色体畸变的几率。结果 FISH诊断膀胱尿路上皮癌的总的敏感度高于尿脱落细胞学检查(分别为79.7%、22.0%,P<0.05),两者的特异度分别为93.3%、100%(P>0.05)。结论 FISH在诊断膀胱尿路上皮癌中敏感性高于尿细胞学检查,同时其特异性亦较高,在早期诊断中具有重要意义。     

荧光原位杂交技术尿脱落细胞检测在上尿路尿路上皮细胞癌诊断中的应用价值

目的 探讨荧光原位杂交技术( FISH)尿脱落细胞检测在上尿路尿路上皮细胞癌诊断中的应用价值.方法 病理诊断为上尿路尿路上皮细胞癌患者30例,留取新鲜晨尿,行FISH和尿脱落细胞学检查,并行多层螺旋CT和彩色多普勒超声检查;留取20例肾癌、6例输尿管结石和4例输尿管狭窄患者的尿液作对照,统计学分析FISH和尿脱落细胞学检查诊断的特征值.结果 FISH、尿脱落细胞学、CT和超声检查诊断上尿路尿路上皮细胞癌的敏感性分别为87％( 26/30)、37％(11/30)、90％(27/30)和43％ (13/30),FISH和CT诊断敏感性差异无统计学意义(P＞0.05),但明显高于超声和尿脱落细胞学检查(P＜0.05);FISH和尿脱落细胞学检查诊断的特异性分别为97％(29/30)和93％ (28/30),二者比较差异无统计学意义(P＞0.05).FISH和尿脱落细胞学检查阳性预测值分别为96％(26/27)和85％ (11/13),阴性预测值分别为88％(29/33)和60％( 28/47).结论 FISH诊断上尿路尿路上皮细胞癌具有较高的敏感性、特异性、阳性预测值和阴性预测值,可作为上尿路尿路上皮细胞癌诊断和术后随访检查的有效方法.     

荧光原位杂交技术在膀胱尿路上皮癌中的临床应用研究

目的:本研究旨在利用荧光原位杂交技术(FISH)辅助诊断膀胱尿路上皮癌,以探讨其作为一种替代尿脱落细胞学的无创性检查在膀胱尿路上皮癌诊断中的应用价值。方法:收集30例健康志愿者的新鲜尿液,应用3、7、17号染色体及9号染色体p16位点探针标记,进行FISH检测,建立正常人群阈值;再收集95例因血尿或影像学检查拟诊为膀胱肿瘤的患者晨尿标本,分别作常规尿脱落细胞学检查和FISH检测,其中79例膀胱镜下活检或术后标本病理确诊为膀胱尿路上皮癌。FISH检测统计目标染色体畸变情况,并进一步分析与病理分级的关系。结果:FISH检测设定的正常阈值为3号染色体:3%;7号染色体:4%;17号染色体:3%;9号染色体p16位点:10%。FISH检测技术的敏感性为74.68%(59/79),高于尿脱落细胞学检查的35.44%(28/79),差异具有统计学意义(P>0.001),而FISH检测的特异性为93.75%(15/16),尿脱落细胞学检查特异性为87.50%(14/16),两者差异无统计学意义(P>0.05)。不同病理分级下FISH检测的敏感性呈现为高级别高阳性率:低度恶性倾向的尿路上皮肿瘤为58.33%(7/12),尿路上皮癌Ⅰ级为54.17%(13/24),尿路上皮癌Ⅰ～Ⅱ级为86.36%(19/22),尿路上皮癌Ⅱ级和Ⅱ～Ⅲ级为94.44%(17/18),尿路上皮癌Ⅲ级为100%(3/3),敏感性随着病理分级的提高而呈现增高趋势。结论:FISH检测技术具备无创、高敏感性的特点,优于传统的尿脱落细胞学检查。不同分级的膀胱尿路上皮肿瘤其FISH检测的敏感性不同,表现为高级别高敏感性。FISH检测上述位点在低级别膀胱尿路上皮肿瘤中敏感性较高,大大提高了低级别尿路上皮肿瘤的检出率,有望成为一种常规的膀胱肿瘤复查指标。     

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.     

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。     

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。     

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。     

NMP22联合尿脱落细胞学检测在膀胱癌术后复发监测中的价值

目的：探讨尿核基质蛋白22（NMP22）联合尿脱落细胞学榆测对膀胱移行细胞癌诊断及术后复发监测中的应用价值。方法：采用酶联免疫法（EI。ISA）检测60例膀胱癌者、20例非膀胱癌者、20例健康志愿者尿中NMP22水平,并同时行尿脱落细胞学检查,并对结果进行比较。结果：膀胱癌者NMP22平均为35．6×10^3U／L,高于非膀胱癌者（7．8×10^3U／L）和健康志愿者（7．2×10^3U／L,P〈0．05）;膀胱癌复发患者（31．5×10^3U／L）高于未复发患者（8．O×10^3U／L,P〈0．05）;膀胱癌者NMP22的敏感性高于尿脱落细胞学,而其特异性低于尿脱落细胞学。结论：尿NMP22对膀胱移行细胞癌具有高灵敏度和无创伤性,是检测膀胱移行细胞癌的有效标志物;联合尿细胞学检查可进一步提高膀胱癌术后复发的诊断率。     

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).     

膀胱移行细胞癌患者尿脱落细胞中生存素的检测及其意义

目的:探讨膀胱移行细胞癌(TCCB)患者尿脱落细胞生存素(Survivin)蛋白和mRNA表达及其临床意义。方法:采用免疫组化SP法和巢式逆转录聚合酶链反应方法,对TCCB患者32例(TCCB组)、非TCCB16例(对照组)尿脱落细胞Survivin的蛋白和mRNA进行检测,同时行尿脱落细胞学检查。结果:TCCB组尿脱落细胞Survivin的蛋白、mRNA阳性表达率分别为28例(87.5%),32例(100%);对照组仅1例mRNA阳性表达(6.2%)。两组Survivin阳性率比较差异有统计学意义(P<0.01);尿液中Survivin的敏感性和特异性,分别为87.5%,80%和96.9%,93.8%。而尿脱落细胞阳性率为18例(56.2%),其敏感性和特异性分别为56.2%和100%。结论:尿脱落细胞Survivin检测诊断TCCB的敏感性和特异性均较高,且对患者无创、无痛苦,可作为早期诊断TCCB的敏感指标,其中RT-PCR检测敏感性更高。     

Value of exfoliative cytology of the urinary bladder in occult bladder cancer and in the control of treated cancers

The exfoliative cytology of the urinary bladder is helpful in the detection of occult bladder carcinoma, which in according to definition is not recognizable without magnification, as well as in the follow-up of treated bladder carcinoma. Within a period of 5 years 23 occult bladder carcinomas were detected by cytological studies alone. The degree of malignancy of the established transitional cell carcinoma varied between G2 and G3. The latent period between the found cytological result and the histological confirmation amounted to 14 months. In our experience the diagnosis of occult bladder carcinoma can be established by exfoliative cytology of the urinary bladder, if invisible parts of tumor with moderate and high degree of malignancy communicate with the mucosa of the bladder. The cytological recognition of malignant cells of urothelium offers valuable support for further therapeutic procedures, if there is no cystoscopic evidence of tumor in the bladder. In addition to clinical diagnosis of bladder cancer exfoliative cytology of the urinary bladder should also be part of the follow-up of treated bladder cancer.     

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 evaluation of basic fetoprotein in bladder cancer

PURPOSE: The early diagnosis of bladder cancer allows for effective local treatment and optimizes the success of surgical therapy. Basic fetoprotein (BFP), measured using a rapid latex immuno-agglutination method, was introduced for the detection of transitional cell carcinoma. The objective of this study was to determine whether there was a correlation between urine BFP level and the grade or stage of bladder cancer, and whether the level could serve as a biochemical marker of bladder cancer. MATERIALS AND METHODS: Single voided specimens were obtained from 66 patients with confirmed or suspicious bladder cancer on cystoscopy, urine cytology or BFP. Each sample was divided into 3 aliquots of which 1 was for urine analysis, 1 was tested for BFP according to latex immunoagglutination method and 1 was sent for cytological examination. All patients subsequently underwent bladder biopsy. RESULTS: There were 54 (82%) patients with biopsy confirmed bladder cancer and 12 (18%) with benign conditions of the bladder. Overall sensitivity with BFP and urine cytology was 38.9% and 48.1% respectively. Specificity was 58.3% and 75.0%, and positive predictive value was 80.8% and 89.7%, respectively. The positive rate of BFP and cytology was higher in invasive cancer (75% and 100%, respectively) than in superficial cancer (36% and 28%). There was no correlation between BFP level and tumor grade, while cytology had a strong association. Linear regression analysis showed the significant correlation between BFP level and tumor size (r = 0.695, p < 0.0001). The detection rate of bladder cancer was higher by the combination of BFP and cytology than by using alone. CONCLUSIONS: BFP in conjunction with urine cytology can increase the detection rate of bladder cancer. But BFP alone cannot be used as a screening test for bladder cancer.