尿细胞角蛋白检测在尿路移行细胞癌诊断和复发监测中的应用研究0_5.doc
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尿细胞角蛋白检测在尿路移行细胞癌诊断和复发监测中的应用研究
李涛 何延瑜 陈梓甫 张延榕 高祥勋 黄超 叶烈夫 黄世清 刘春 陈文榜 詹汉雄 詹天棋
福建省立医院泌尿外科(福州，350001 Tel:13705078075)
[摘要] 目的 评价尿细胞角蛋白(CK)检测在尿路移行细胞癌(TCC)诊断和复发监测中的应用价值。 方法 采用ELISA法检测244例尿路TCC及292例泌尿系非TCC患者尿液中CK8和18的含量(UBC值)，应用受试者作业特征曲线(ROC)选择尿CK诊断尿路TCC和监测膀胱癌术后复发的最适临界值。结果 TCC患者尿UBC均值为30.2μg/L, 与泌尿系非TCC患者8.9μg/L的均值比较, 差异有极显著性意义(P<0.001)。ROC曲线(曲线下面积为0.821)确定以8.4μg/L为最适临界值, 尿CK诊断TCC的敏感性为76.6%，特异性为74.3%，阳性预测值为71.4%，阴性预测值为79.2%。32例上尿路TCC和110例非TCC的上尿路疾病患者尿UBC均值分别为20.9μg/L和9.0μg/L(P<0.001)，以8.4μg/L为临界值, 尿CK诊断上尿路TCC的敏感性为78.1%，特异性为71.8%。212例膀胱TCC中，尿UBC值与肿瘤数目(单发或多发)不相关(P=0.415)，但与肿瘤大小(多发肿瘤以最大径之和表示)密切相关(Pearson相关分析，r＝0.342，P<0.001)。组织学分级G1、G2、G3肿瘤患者尿UBC均值分别为23.8μg/L、33.6μg/L和38.4μg/L(P＝0.763)，以8.4μg/L为临界值时尿CK诊断各级TCC的敏感性分别为68.2%、76.6%和88.1%(P＝0.064)。浅表性(Ta～T1)和浸润性(T2～T4)TCC患者尿UBC均值分别为24.4μg/L和47.3μg/L(P<0.001)，以8.4μg/L为临界值时尿CK诊断敏感性分别为69.7%和91.0%(P＝0.001)。ROC曲线分析表明，对已活检确诊的膀胱TCC，尿UBC取13.55μg/L为临界值时诊断浸润癌的敏感性为76.1%，特异性为62.8%，当取25.0μg/L为临界值时敏感性降为52.2%，但特异性达80.0%。膀胱初发性TCC和复发性TCC患者的尿UBC均值分别为22.0μg/L和57.7μg/L(P<0.001)，以8.4μg/L为临界值时尿CK诊断敏感性分别为70.3%和93.0%(P<0.001)。76例膀胱TCC术后膀胱镜检查未见肿瘤复发的患者尿UBC均值为10.5μg/L，与复发瘤比较，差异有极显著性意义(P<0.001)。ROC曲线分析表明，对膀胱TCC术后随访复查时，尿CK取14.6μg/L为临界值时诊断复发癌的敏感性为87.7%，特异性为86.8%；当取11.65μg/L为临界值时敏感性达93%，特异性为78.9%；当取37.5μg/L为临界值时，虽然敏感性仅为43.9%，但假阳性率仅为3.9%。 结论 尿CK检测对尿路TCC的诊断是一种较为敏感、特异且无创的方法，对膀胱TCC的临床分期和术后复发癌的监测有一定应用价值。与影像学和尿细胞学等其它诊断方法相结合，可提高上尿路病变诊断的准确性。
[关键词] 癌，移行细胞； 角蛋白； 膀胱肿瘤； 诊断，实验室
Evaluation of urinary cytokeratin 8 and 18 as a diagnostic marker for transitional cell carcinoma LI Tao, HE Yanyu, CHEN Zifu, ZHANG Yanrong, GAO Xiangxun, HUANG Chao, YE Liefu, HUANG Shiqing, LIU Chun, CHEN Wenbang, ZHAN Hanxiong, ZHAN Tianqi. Department of Urology, Fujian Provincial Hospital, Fuzhou 350001, China
[Abstract] Objective To determine the clinical efficacy of cytokeratin 8 and 18 as a novel urine marker for transitional cell carcinoma (TCC). Methods Urinary concentrations of cytokeratin 8 and 18 (urinary bladder cancer antigen, UBC) were determined for 244 cases of TCC and 292 cases of other urological conditions by an enzyme-linked immunosorbent assay (ELISA). Results The UBC concentrations of the TCC patients (mean 30.2μg/L) were significantly higher than the patients without TCC (mean 8.9μg/L)(P<0.001). At a threshold value of 8.4μg/l, the sensitivity of UBC for detection of TCC was 76.6%, the specificity was 74.3%, the positive predictive value was 71.4%, and the negative predictive value was 79.2%. The mean UBC concentrations of 32 cases of TCC and 110 cases of nonurothelial cancer diseases of the upper urinary tract were 20.9μg/L and 9.0μg/L,respectively(P<0.001). At a threshold value of 8.4μg/l, the sensitivity of UBC for detection of TCC of the upper urinary tract was 78.1%, and the specificity was 71.8%. No significant difference was found between the UBC values of the single tumors and the multiple tumors(P=0.415) , but significant corelation was found between the UBC values and the tumor size of 212 cases of bladder TCCs (Pearson corelation ......
尿细胞角蛋白检测在尿路移行细胞癌诊断和复发监测中的应用研究
李涛 何延瑜 陈梓甫 张延榕 高祥勋 黄超 叶烈夫 黄世清 刘春 陈文榜 詹汉雄 詹天棋
福建省立医院泌尿外科(福州，350001 Tel:13705078075)
[摘要] 目的 评价尿细胞角蛋白(CK)检测在尿路移行细胞癌(TCC)诊断和复发监测中的应用价值。 方法 采用ELISA法检测244例尿路TCC及292例泌尿系非TCC患者尿液中CK8和18的含量(UBC值)，应用受试者作业特征曲线(ROC)选择尿CK诊断尿路TCC和监测膀胱癌术后复发的最适临界值。结果 TCC患者尿UBC均值为30.2μg/L, 与泌尿系非TCC患者8.9μg/L的均值比较, 差异有极显著性意义(P<0.001)。ROC曲线(曲线下面积为0.821)确定以8.4μg/L为最适临界值, 尿CK诊断TCC的敏感性为76.6%，特异性为74.3%，阳性预测值为71.4%，阴性预测值为79.2%。32例上尿路TCC和110例非TCC的上尿路疾病患者尿UBC均值分别为20.9μg/L和9.0μg/L(P<0.001)，以8.4μg/L为临界值, 尿CK诊断上尿路TCC的敏感性为78.1%，特异性为71.8%。212例膀胱TCC中，尿UBC值与肿瘤数目(单发或多发)不相关(P=0.415)，但与肿瘤大小(多发肿瘤以最大径之和表示)密切相关(Pearson相关分析，r＝0.342，P<0.001)。组织学分级G1、G2、G3肿瘤患者尿UBC均值分别为23.8μg/L、33.6μg/L和38.4μg/L(P＝0.763)，以8.4μg/L为临界值时尿CK诊断各级TCC的敏感性分别为68.2%、76.6%和88.1%(P＝0.064)。浅表性(Ta～T1)和浸润性(T2～T4)TCC患者尿UBC均值分别为24.4μg/L和47.3μg/L(P<0.001)，以8.4μg/L为临界值时尿CK诊断敏感性分别为69.7%和91.0%(P＝0.001)。ROC曲线分析表明，对已活检确诊的膀胱TCC，尿UBC取13.55μg/L为临界值时诊断浸润癌的敏感性为76.1%，特异性为62.8%，当取25.0μg/L为临界值时敏感性降为52.2%，但特异性达80.0%。膀胱初发性TCC和复发性TCC患者的尿UBC均值分别为22.0μg/L和57.7μg/L(P<0.001)，以8.4μg/L为临界值时尿CK诊断敏感性分别为70.3%和93.0%(P<0.001)。76例膀胱TCC术后膀胱镜检查未见肿瘤复发的患者尿UBC均值为10.5μg/L，与复发瘤比较，差异有极显著性意义(P<0.001)。ROC曲线分析表明，对膀胱TCC术后随访复查时，尿CK取14.6μg/L为临界值时诊断复发癌的敏感性为87.7%，特异性为86.8%；当取11.65μg/L为临界值时敏感性达93%，特异性为78.9%；当取37.5μg/L为临界值时，虽然敏感性仅为43.9%，但假阳性率仅为3.9%。 结论 尿CK检测对尿路TCC的诊断是一种较为敏感、特异且无创的方法，对膀胱TCC的临床分期和术后复发癌的监测有一定应用价值。与影像学和尿细胞学等其它诊断方法相结合，可提高上尿路病变诊断的准确性。
[关键词] 癌，移行细胞； 角蛋白； 膀胱肿瘤； 诊断，实验室
Evaluation of urinary cytokeratin 8 and 18 as a diagnostic marker for transitional cell carcinoma LI Tao, HE Yanyu, CHEN Zifu, ZHANG Yanrong, GAO Xiangxun, HUANG Chao, YE Liefu, HUANG Shiqing, LIU Chun, CHEN Wenbang, ZHAN Hanxiong, ZHAN Tianqi. Department of Urology, Fujian Provincial Hospital, Fuzhou 350001, China
[Abstract] Objective To determine the clinical efficacy of cytokeratin 8 and 18 as a novel urine marker for transitional cell carcinoma (TCC). Methods Urinary concentrations of cytokeratin 8 and 18 (urinary bladder cancer antigen, UBC) were determined for 244 cases of TCC and 292 cases of other urological conditions by an enzyme-linked immunosorbent assay (ELISA). Results The UBC concentrations of the TCC patients (mean 30.2μg/L) were significantly higher than the patients without TCC (mean 8.9μg/L)(P<0.001). At a threshold value of 8.4μg/l, the sensitivity of UBC for detection of TCC was 76.6%, the specificity was 74.3%, the positive predictive value was 71.4%, and the negative predictive value was 79.2%. The mean UBC concentrations of 32 cases of TCC and 110 cases of nonurothelial cancer diseases of the upper urinary tract were 20.9μg/L and 9.0μg/L,respectively(P<0.001). At a threshold value of 8.4μg/l, the sensitivity of UBC for detection of TCC of the upper urinary tract was 78.1%, and the specificity was 71.8%. No significant difference was found between the UBC values of the single tumors and the multiple tumors(P=0.415) , but significant corelation was found between the UBC values and the tumor size of 212 cases of bladder TCCs (Pearson corelation ......
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