尿核基质蛋白-22和膀胱肿瘤抗原检测与尿脱落细胞学检查在膀胱癌检测及随访中的比较：假阳性结果的预后价值

A comparison of urinary nuclear matrix protein-22 and bladder tumour antigen tests with voided urinary cytology in detecting and following bladder cancer: the prognostic value of false-positive results.

作者信息

Poulakis V, Witzsch U, De Vries R, Altmannsberger H M, Manyak M J, Becht E

机构信息

Department of Urology and Paediatric Urology, Hospital Nordwest, Academic Hospital of Johann-Wolfgang-Goethe-University Frankfurt, Frankfurt/Main, Germany.

出版信息

BJU Int. 2001 Nov;88(7):692-701. doi: 10.1046/j.1464-410x.2001.02355.x.

DOI:10.1046/j.1464-410x.2001.02355.x

PMID:11890239

Abstract

OBJECTIVES

To evaluate the diagnostic and prognostic value of the nuclear matrix protein-22 (NMP22) and bladder tumour antigen (BTAstat) tests compared with voided urinary cytology (VUC) in detecting and following bladder cancer, assessing particularly the prognostic value of false-positive test results in patients followed up for bladder cancer.

PATIENTS AND METHODS

From 739 patients suspected of having bladder cancer, voided urine samples for the NMP22 and BTAstat tests, and for VUC and urine analysis, were collected before cystoscopy. All patients underwent transurethral resection of bladder lesions or mapping. and were followed for a mean (range) of 27.3 (3-65) months.

RESULTS

In the 406 patients with bladder cancer, the overall sensitivity was 85% for NMP22, 70% for BTAstat and 62% for VUC. For histological grades 1-3 the sensitivity in detecting transitional cell carcinoma was 82%, 89% and 94% for NMP22, 53%, 76% and 90% for BTAstat, and 38%, 68% and 90% for VUC, respectively. Although the sensitivity in detecting invasive carcinoma was >85% for all the tests. NMP22 and BTAstat were statistically more sensitive than VUC for superficial tumours. The optimal threshold value for NMP22, calculated using the receiver operating characteristics curve was 8.25 U/mL. The specificity was 68% for NMP22, 67% for BTAstat, and 96% for VUC. The specificity of VUC remained >87% and was independent of benign histological findings. In contrast, in patients with no apparent genitourinary disease on histology, NMP22 and BTAstat had significantly higher specificity (94% and 92%, respectively: P=0.003) than in the group with chronic cystitis (52% for both tests). Forty patients having no bladder cancer at biopsy had a recurrence after a mean (range) follow-up of 7.7 (3-15) months: all had a previous history of bladder cancer. According to subsequent recurrence, the prognostic positive and negative predictive values were 18% and 91% for NMP22, 13% and 88% for BTAstat, and 79% and 91% for VUC. Both false-positive VUC and NMP22 tests predicted recurrence (log-rank test, P<0.001 and P=0.004, respectively), but the BTAstat test produced no similar correlation (P=0.778).

CONCLUSION

The NMP22 and BTAstat tests are better than VUC for detecting superficial and low-grade bladder cancer but they have significantly lower specificity. After excluding diseases with the potential to interfere in these tests the overall specificity of both tests is increased considerably. False-positive results from NMP22 and VUC but not from BTAstat in patients followed up for bladder cancer correlate with future recurrences.

摘要

目的

评估核基质蛋白-22（NMP22）和膀胱肿瘤抗原（BTAstat）检测与排尿细胞学检查（VUC）相比，在膀胱癌检测及随访中的诊断和预后价值，尤其评估膀胱癌随访患者中假阳性检测结果的预后价值。

患者与方法

对739例疑似膀胱癌患者，在膀胱镜检查前采集排尿样本进行NMP22和BTAstat检测、VUC及尿液分析。所有患者均接受经尿道膀胱病变切除术或膀胱病变定位检查，并随访平均（范围）27.3（3 - 65）个月。

结果

在406例膀胱癌患者中，NMP22的总体敏感性为85%，BTAstat为70%，VUC为62%。对于组织学1 - 3级，NMP22检测移行细胞癌的敏感性分别为82%、89%和94%，BTAstat为53%、76%和90%，VUC为38%、68%和90%。尽管所有检测对浸润性癌的敏感性均>85%，但对于浅表肿瘤，NMP22和BTAstat在统计学上比VUC更敏感。使用受试者工作特征曲线计算得出NMP22的最佳阈值为8.25 U/mL。NMP22的特异性为68%，BTAstat为67%，VUC为96%。VUC的特异性保持>87%，且与良性组织学结果无关。相比之下，组织学上无明显泌尿生殖系统疾病的患者中，NMP22和BTAstat的特异性（分别为94%和92%：P = 0.003）显著高于慢性膀胱炎组（两种检测均为52%）。40例活检时无膀胱癌的患者在平均（范围）7.7（3 - 15）个月的随访后复发：所有患者既往均有膀胱癌病史。根据后续复发情况，NMP22的预后阳性和阴性预测值分别为18%和91%，BTAstat为13%和88%，VUC为79%和91%。VUC和NMP22的假阳性检测结果均预测了复发（对数秩检验，P分别<0.001和P = 0.004），但BTAstat检测未显示类似相关性（P = 0.778）。