Department of Pathology and Cancer Institute, University College London, London, United Kingdom.
PLoS One. 2012;7(7):e40305. doi: 10.1371/journal.pone.0040305. Epub 2012 Jul 9.
Urinary biomarkers for bladder cancer detection are constrained by inadequate sensitivity or specificity. Here we evaluate the diagnostic accuracy of Mcm5, a novel cell cycle biomarker of aberrant growth, alone and in combination with NMP22.
1677 consecutive patients under investigation for urinary tract malignancy were recruited to a prospective blinded observational study. All patients underwent ultrasound, intravenous urography, cystoscopy, urine culture and cytologic analysis. An immunofluorometric assay was used to measure Mcm5 levels in urine cell sediments. NMP22 urinary levels were determined with the FDA-approved NMP22® Test Kit.
Genito-urinary tract cancers were identified in 210/1564 (13%) patients with an Mcm5 result and in 195/1396 (14%) patients with an NMP22 result. At the assay cut-point where sensitivity and specificity were equal, the Mcm5 test detected primary and recurrent bladder cancers with 69% sensitivity (95% confidence interval = 62-75%) and 93% negative predictive value (95% CI = 92-95%). The area under the receiver operating characteristic curve for Mcm5 was 0.75 (95% CI = 0.71-0.79) and 0.72 (95% CI = 0.67-0.77) for NMP22. Importantly, Mcm5 combined with NMP22 identified 95% (79/83; 95% CI = 88-99%) of potentially life threatening diagnoses (i.e. grade 3 or carcinoma in situ or stage ≥pT1) with high specificity (72%, 95% CI = 69-74%).
The Mcm5 immunoassay is a non-invasive test for identifying patients with urothelial cancers with similar accuracy to the FDA-approved NMP22 ELISA Test Kit. The combination of Mcm5 plus NMP22 improves the detection of UCC and identifies 95% of clinically significant disease. Trials of a commercially developed Mcm5 assay suitable for an end-user laboratory alongside NMP22 are required to assess their potential clinical utility in improving diagnostic and surveillance care pathways.
用于膀胱癌检测的尿生物标志物存在敏感性或特异性不足的问题。在此，我们评估了 Mcm5 的诊断准确性，Mcm5 是一种新型的细胞周期异常生长生物标志物，单独使用和与 NMP22 联合使用时的诊断准确性。
1677 名连续接受尿路恶性肿瘤检查的患者被纳入前瞻性、盲法观察性研究。所有患者均接受超声、静脉尿路造影、膀胱镜检查、尿液培养和细胞学分析。免疫荧光分析用于测量尿液细胞沉淀物中的 Mcm5 水平。NMP22 尿液水平采用 FDA 批准的 NMP22®检测试剂盒进行测定。
在有 Mcm5 检测结果的 1564 例患者中有 210 例（13%）和在有 NMP22 检测结果的 1396 例患者中有 195 例（14%）发现泌尿生殖系统癌症。在检测的检测点处，当敏感性和特异性相同时，Mcm5 检测对原发性和复发性膀胱癌的检出率为 69%（95%置信区间为 62-75%）和 93%的阴性预测值（95%CI=92-95%）。Mcm5 的受试者工作特征曲线下面积为 0.75（95%CI=0.71-0.79），NMP22 的曲线下面积为 0.72（95%CI=0.67-0.77）。重要的是，Mcm5 联合 NMP22 可识别 95%（79/83；95%CI=88-99%）的潜在危及生命的诊断（即 3 级或原位癌或≥pT1 期），特异性为 72%（95%CI=69-74%）。
Mcm5 免疫分析是一种非侵入性检测方法，用于识别尿路上皮癌患者，其准确性与 FDA 批准的 NMP22 ELISA 检测试剂盒相似。Mcm5 加 NMP22 的联合使用可提高 UCC 的检出率，并可识别 95%的具有临床意义的疾病。需要对一种适合终端用户实验室的商业化开发的 Mcm5 检测方法与 NMP22 进行联合评估，以评估它们在改善诊断和监测护理途径方面的潜在临床应用价值。
