NMP-22、端粒酶和BTA在膀胱癌检测中的比较研究。

Comparative study of NMP-22, telomerase, and BTA in the detection of bladder cancer.

作者信息

Abd El Gawad Iman A, Moussa Heba S, Nasr Maha I, El Gemae Emad H, Masooud Amr M, Ibrahim Ibrahim K, El Hifnawy Niveen M

机构信息

The Department of Clinical & Chemical Pathology, NCI, Cairo University.

出版信息

J Egypt Natl Canc Inst. 2005 Sep;17(3):193-202.

PMID:16799657

Abstract

PURPOSE

The diagnostic efficacy of Nuclear Matrix Protein-22 (NMP-22), bladder tumor antigen (BTA TRAK), and telomerase activity was evaluated in urine in a trial to assess their value in the detection of bladder cancer and to compare it to that of routine urine cytology.

SUBJECTS AND METHODS

The study included 46 newly diagnosed bladder cancer patients, diagnosed by cystoscopy and histopathological typing, in addition to 20 patients with benign bladder lesions and 20 healthy age and sex matched volunteers as a control group. Fifty percent of the cancer patients (23/46) had proven bilharzial history. Most patients (27/46) had transitional cell carcinoma (TCC), 17/46 had squamous cell carcinoma (SCC), while only 2 patients had adenocarcinoma. A single freshly voided urine sample (approximately 100ml) was collected from each patient and control subject and aliquoted for each test. All assays were conducted according to the manufacturer's guidelines and the results were compared to those of urine cytology.

RESULTS

The optimal cutoffs for NMP-22, BTA and telomerase activity as calculated by ROC curves were 12.1 U/ml, 78 U/ml, 0.48 (Ratio) respectively. The levels of the three parameters were significantly higher in the malignant group compared to either the benign group or normal controls, (p<0.001) and the positive rates were also higher in the malignant group for all 3 parameters. The overall sensitivity of urine cytology, NMP-22, BTA and telomerase was 54.3%, 91.3%, 100% and 80.4% respectively. For bilharzial cancer bladder respective sensitivities were 69.6%, 95.6%, 100% and 73.9%, while for nonbilharzial cancer bladder the respective sensitivities were 39.1%, 87%, 100% and 87%. The overall specificities with urine cytology, NMP-22, BTA and telomerase was 100%, 87.5%, 92.5% and 95.0%, respectively. Combined sensitivity of voided urine cytology with one or more of the 3 biomarkers, or the use of these biomarkers in double or triple combinations gave higher positivity than each biomarker alone.

CONCLUSION

BTA showed the highest sensitivity in all the studied parameters in the bladder cancer group, bilharzial bladder cancer subgroup, and non bilharzial bladder subgroup, (100%), while the highest specificity was recorded with urine cytology (100%), followed by telomerase (95%), then BTA (92.5%), and lastly NMP- 22 (87.5%). Use of markers in combination with cytology, or in a panel, improved the sensitivity, and specificity.

摘要

目的

在一项试验中评估核基质蛋白22（NMP - 22）、膀胱肿瘤抗原（BTA TRAK）和端粒酶活性在尿液中的诊断效能，以评估它们在膀胱癌检测中的价值，并与常规尿细胞学检查进行比较。

受试者与方法

该研究纳入了46例新诊断的膀胱癌患者，通过膀胱镜检查和组织病理学分型确诊，另外还有20例膀胱良性病变患者以及20例年龄和性别匹配的健康志愿者作为对照组。50%的癌症患者（23/46）有确诊的血吸虫病史。大多数患者（27/46）患有移行细胞癌（TCC），17/46患有鳞状细胞癌（SCC），而只有2例患者患有腺癌。从每位患者和对照受试者收集一份新鲜晨尿样本（约100ml），并对每份样本进行分装用于各项检测。所有检测均按照制造商的指南进行，并将结果与尿细胞学检查结果进行比较。

结果

通过ROC曲线计算得出，NMP - 22、BTA和端粒酶活性的最佳截断值分别为12.1 U/ml、78 U/ml、0.48（比值）。与良性组或正常对照组相比，恶性组中这三个参数的水平显著更高（p<0.001），并且恶性组中这三个参数的阳性率也更高。尿细胞学检查、NMP - 22、BTA和端粒酶的总体敏感性分别为54.3%、91.3%、100%和80.4%。对于血吸虫性膀胱癌，各自的敏感性分别为69.6%、95.6%、100%和73.9%，而对于非血吸虫性膀胱癌，各自的敏感性分别为39.1%、87%、100%和87%。尿细胞学检查、NMP - 22、BTA和端粒酶的总体特异性分别为100%、87.5%、92.5%和95.0%。晨尿细胞学检查与三种生物标志物中的一种或多种联合使用，或者将这些生物标志物进行双重或三重组合使用，其阳性率均高于单独使用每种生物标志物。

结论

在膀胱癌组、血吸虫性膀胱癌亚组和非血吸虫性膀胱癌亚组的所有研究参数中，BTA显示出最高的敏感性（100%），而尿细胞学检查的特异性最高（100%），其次是端粒酶（95%），然后是BTA（92.5%），最后是NMP - 22（87.5%）。将标志物与细胞学检查联合使用或组成检测组合，可提高敏感性和特异性。