p53结合蛋白1的表达模式是膀胱尿路上皮癌基因组不稳定性的新分子指标。,Scientific Reports

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p53结合蛋白1的表达模式是膀胱尿路上皮癌基因组不稳定性的新分子指标。
Scientific Reports ( IF 3.8 ) Pub Date : 2018-10-19 , DOI: 10.1038/s41598-018-33761-9
Katsuya Matsuda ₁ , Tatsuhiko Kawasaki ₂ , Yuko Akazawa ₃ , Yuhmi Hasegawa ₄ , Hisayoshi Kondo ₅ , Keiji Suzuki ₆ , Masachika Iseki ₂ , Masahiro Nakashima ₁

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拷贝数的改变和杂合性的丧失与肿瘤分级和膀胱癌分期的增加有关。我们以前的研究表明，Ki-67和p53结合蛋白1（53BP1）的共表达可以提供异常DNA损伤反应（DDR）途径的指示。本研究调查了使用膀胱组织在尿路上皮癌（UC）中将53BP1表达作为新型分子标记，总共有40例病例，包括正常尿路上皮，尿路上皮乳头瘤，低度UC或高度UC。使用双标记免疫荧光分析53BP1和Ki-67表达。将其与染色体不稳定性水平以及其他DDR分子催化亚基的表达进行了比较。这项研究确定了尿路上皮癌变过程中53BP1表达模式的明显差异，以及它们与基因组不稳定性的紧密联系。53BP1异常的免疫反应性，特别是与Ki-67的共定位，仅限于恶性组织。我们的分析表明，超过53％的具有53BP1异常表达和Ki-67免疫反应性的细胞核可将高级别UC与低级别UC区分为80.0％的敏感性和100％的特异性。因此，我们建议对53BP1和Ki-67表达进行双重免疫荧光分析可以提供一个有用的工具，以评估尿路上皮肿瘤的染色体不稳定和恶性潜能。具有53BP1异常表达和Ki-67免疫反应性的4％的细胞核将高级别UC与低级别UC区别开，灵敏度为80.0％，特异性为100％。因此，我们建议对53BP1和Ki-67表达进行双重免疫荧光分析可以提供一个有用的工具，以评估尿路上皮肿瘤的染色体不稳定和恶性潜能。具有53BP1异常表达和Ki-67免疫反应性的4％的细胞核将高级别UC与低级别UC区别开，灵敏度为80.0％，特异性为100％。因此，我们建议对53BP1和Ki-67表达进行双重免疫荧光分析可以提供一个有用的工具，以评估尿路上皮肿瘤的染色体不稳定和恶性潜能。

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Expression pattern of p53-binding protein 1 as a new molecular indicator of genomic instability in bladder urothelial carcinoma.

Copy number alterations and loss of heterozygosity are associated with increasing tumor grade and bladder cancer stage. Our previous study suggested that co-expression of Ki-67 and p53-binding protein 1 (53BP1) could provide an indicator of an abnormal DNA damage response (DDR) pathway. The present study investigated 53BP1 expression as a novel molecular marker in urothelial carcinoma (UC) using bladder tissues with in total of 40 cases including a normal urothelium, urothelial papilloma, low-grade UC, or high-grade UC. Double-label immunofluorescence was used to analyze 53BP1 and Ki-67 expression. This was compared with the level of chromosomal instability and with the expression of other DDR molecules catalytic subunit. This study identified clear differences in the 53BP1 expression patterns in urothelial carcinogenesis, and their close association with genomic instability. 53BP1 abnormal immunoreactivity, particularly with co-localization of Ki-67, was restricted to malignant tissues. Our analyses indicated that a cut-off of >4% of nuclei with 53BP1 abnormal expression plus Ki-67 immunoreactivity distinguished high-grade UC from low-grade UC with 80.0% sensitivity and 100% specificity. We therefore propose that double immunofluorescent analysis of 53BP1 and Ki-67 expression could provide a useful tool to estimate the chromosomal instability and malignant potential of urothelial tumors.

更新日期：2018-10-19

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