膀胱癌的四种肿瘤标志物——组织多肽抗原（TPA）、HER-2/neu（ERB B2）、尿激酶型纤溶酶原激活物受体（uPAR）和TP53突变。

Four tumour markers for urinary bladder cancer--tissue polypeptide antigen (TPA), HER-2/neu (ERB B2), urokinase-type plasminogen activator receptor (uPAR) and TP53 mutation.

作者信息

Ecke Thorsten H, Schlechte Horst H, Schulze Guntram, Lenk Severin V, Loening Stefan A

机构信息

Department of Urology, HUMAINE Hospital Bad Saarow, Germany.

出版信息

Anticancer Res. 2005 Jan-Feb;25(1B):635-41.

PMID:15816639

Abstract

PURPOSE

Tissue polypeptide antigen (TPA) is present in the proteolytic fragments of cytokeratins 8, 18 and 19 as a component of the cytoskeleton of nonsquamous epithelia. HER-2/neu protein is a transmembrane tyrosine kinase cell surface growth factor receptor that is expressed on normal epithelial and some cancer cells. The urokinase-type plasminogen activator receptor (uPAR) is a GPI-linked single-chain glycoprotein. Mutations of the tumour suppressor gene P53 (TP53) are frequently correlated with tumour development and progression. We compared TPA, HER-2/neu and uPAR, and TP53 mutation in tumour-free and bladder cancer patients.

MATERIALS AND METHODS

Clinical samples were used from 60 patients with tumours of the urinary bladder and from 9 patients with benign urological diseases. TPA was analyzed by the immunoluminometric assay LIA-mat TPA-MProlifigen. HER-2/neu was measured using the Bayer Oncoprotein test. uPAR was measured with the IMUBIND Total uPAR ELISA Kit. Mutation status in TP53 exons 5, 6, 7 and 8 was analyzed by temperature gradient gel electrophoresis of exon-specific PCR products and by sequence analysis. Statistical analysis included ROC, Mann-Whitney U-test and Pearson's correlation.

RESULTS

Pathological concentrations of TPA, HER-2/neu and uPAR are detectable in the serum and in urine of bladder cancer patients. The calculated diagnostic sensitivity for TPA in serum was 68.37%, for TPA in urine 33.3%, for HER-2/neu 86.7% and for uPAR 79.5%. Pathological levels of TPA in serum (p=0.001) and HER-2/neu (p =0.001) were significantly higher in patients with bladder cancer in comparison to the control group. For superficial bladder cancer, the mutation frequency in TP53 was 50%, while for invasive bladder cancer the mutation frequency in TP53 was 100%. Elevated TPA, HER-2/neu and uPAR levels were associated with all grades and stages of bladder cancer.

CONCLUSION

TPA, HER-2/neu or uPAR can differ between bladder cancer patients and the control group, but not between superficial and invasive bladder cancer. TP53 mutation frequently occurs in higher stages of bladder tumours.

摘要

目的

组织多肽抗原（TPA）作为非鳞状上皮细胞骨架的组成部分，存在于细胞角蛋白8、18和19的蛋白水解片段中。HER-2/neu蛋白是一种跨膜酪氨酸激酶细胞表面生长因子受体，在正常上皮细胞和一些癌细胞中表达。尿激酶型纤溶酶原激活物受体（uPAR）是一种糖基磷脂酰肌醇连接的单链糖蛋白。肿瘤抑制基因P53（TP53）的突变常与肿瘤的发生和进展相关。我们比较了无肿瘤患者和膀胱癌患者的TPA、HER-2/neu、uPAR以及TP53突变情况。

材料与方法

使用了60例膀胱肿瘤患者和9例良性泌尿系统疾病患者的临床样本。通过免疫发光分析法LIA-mat TPA-MProlifigen分析TPA。使用拜耳癌蛋白检测法测量HER-2/neu。用IMUBIND总uPAR ELISA试剂盒测量uPAR。通过外显子特异性PCR产物的温度梯度凝胶电泳和序列分析来分析TP53外显子5、6、7和8的突变状态。统计分析包括ROC、曼-惠特尼U检验和皮尔逊相关性分析。

结果

在膀胱癌患者的血清和尿液中可检测到TPA、HER-2/neu和uPAR的病理浓度。计算得出血清中TPA的诊断敏感性为68.37%，尿液中TPA为33.3%，HER-2/neu为86.7%，uPAR为79.5%。与对照组相比，膀胱癌患者血清中TPA（p = 0.001）和HER-2/neu（p = 0.001）的病理水平显著更高。对于浅表性膀胱癌，TP53的突变频率为50%，而浸润性膀胱癌中TP53的突变频率为100%。TPA、HER-2/neu和uPAR水平升高与膀胱癌的所有分级和分期相关。