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两种新型尿液肿瘤标志物:膀胱肿瘤纤连蛋白和细胞角蛋白18用于膀胱癌诊断的评估

Evaluation of two new urinary tumor markers: bladder tumor fibronectin and cytokeratin 18 for the diagnosis of bladder cancer.

作者信息

Sánchez-Carbayo M, Urrutia M, González de Buitrago J M, Navajo J A

机构信息

Laboratorio de Marcadores Tumorales, Servicio de Bioquímica, Hospital Universitario de Salamanca, Spain.

出版信息

Clin Cancer Res. 2000 Sep;6(9):3585-94.

PMID:10999749
Abstract

Our objectives were to evaluate the diagnostic value of two new urinary tumor markers, cytokeratin 18 (CK18) and bladder tumor fibronectin (BTF), for the detection and monitoring of bladder cancer. The study comprised 931 urine samples belonging to 402 subjects: 112 individuals under suspicion for a primary bladder tumor (group 1); 104 bladder cancer patients under scheduled follow-up (group 2); 109 bladder cancer patients receiving intravesical instillations (group 3); 45 patients with other urological diseases (group 4); and 32 healthy subjects (group 5). Voided urine samples were collected before cystoscopies, between them and before intravesical instillations. CK18 and BTF tests were measured by chemiluminescent immunoassays. Optimal receiver operating characteristic cutoffs of 7.4 microg/L for CK18 and 52.8 microg/liter for BTF rendered overall sensitivities of 66.2% for CK18 and 80.0% for BTF at specificities of 88.4 and 74.7%, respectively. Urinary cytology provided a sensitivity of 29.2% at a specificity of 99.1%. Sensitivities were 80.8, 74.2, and 82.3% for BTF and 71.1, 77.4, and 64.7% for CK18 for groups 1 to 3, respectively. False positive rates were higher for BTF in all groups of patients. Elevated urinary tumor markers during the monitoring of patients with bladder cancer could detect recurrence sooner than scheduled cystoscopies. Persistence of negative markers was greatly indicative of free of disease status in follow-up. CK18 and BTF in urine may eventually prove to be of benefit for specific patients with bladder carcinoma given its higher sensitivity compared with cytology. In selected patients, namely those with persistent negative urinary CK18 and BTF, the number of cystoscopies could be reduced.

摘要

我们的目标是评估两种新型尿液肿瘤标志物,即细胞角蛋白18(CK18)和膀胱肿瘤纤连蛋白(BTF),在膀胱癌检测和监测中的诊断价值。该研究包括属于402名受试者的931份尿液样本:112名疑似原发性膀胱肿瘤的个体(第1组);104名计划进行随访的膀胱癌患者(第2组);109名接受膀胱内灌注的膀胱癌患者(第3组);45名患有其他泌尿系统疾病的患者(第4组);以及32名健康受试者(第5组)。在膀胱镜检查前、检查期间以及膀胱内灌注前收集晨尿样本。CK18和BTF检测通过化学发光免疫分析进行测量。CK18的最佳受试者工作特征曲线截断值为7.4微克/升,BTF为52.8微克/升,在特异性分别为88.4%和74.7%时,CK18的总体敏感性为66.2%,BTF为80.0%。尿细胞学检查在特异性为99.1%时的敏感性为29.2%。第1至3组中,BTF的敏感性分别为80.8%、74.2%和82.3%,CK18的敏感性分别为71.1%、77.4%和64.7%。所有患者组中BTF的假阳性率较高。在膀胱癌患者的监测过程中,尿液肿瘤标志物升高比预定的膀胱镜检查能更早地检测到复发。标志物持续阴性在很大程度上表明随访期间无疾病状态。鉴于尿液中的CK18和BTF与细胞学检查相比具有更高的敏感性,它们最终可能对特定的膀胱癌患者有益。在选定的患者中,即尿液CK18和BTF持续阴性的患者,可以减少膀胱镜检查的次数。

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