Expression pattern of p53-binding protein 1 as a new molecular indicator of genomic instability in bladder urothelial carcinoma.
Expression pattern of p53-binding protein 1 as a new molecular indicator of genomic instability in bladder urothelial carcinoma.
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DOI：
10.1038/s41598-018-33761-9
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发表时间：
2018-10-19
影响因子：
4.6
通讯作者：
Nakashima M
中科院分区：
文献类型：
--
作者：
Matsuda K;Kawasaki T;Akazawa Y;Hasegawa Y;Kondo H;Suzuki K;Iseki M;Nakashima M
拷贝数改变和杂合性丢失与肿瘤级别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（53 BP 1）的共表达可以提供一个异常的DNA损伤反应（DDR）途径的指标。本研究使用膀胱组织研究了53 BP 1表达作为尿路上皮癌（UC）的新分子标记物，共40例，包括正常尿路上皮、尿路上皮乳头状瘤、低度UC或高度UC。免疫荧光双标记法检测53 BP 1和Ki-67的表达。这与染色体不稳定性水平和其他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发生过程中53 BP 1表达模式的明显差异，以及它们与基因组不稳定性的密切关系。53 BP 1异常免疫反应性，特别是与Ki-67共定位，仅限于恶性组织。我们的分析表明，具有53 BP 1异常表达和Ki-67免疫反应性的细胞核>4%的临界值区分高级别UC和低级别UC，具有80.0%的灵敏度和100%的特异性。因此，我们建议53 BP 1和Ki-67表达的双重免疫荧光分析可以提供一个有用的工具，以估计染色体不稳定性和恶性潜能的尿路上皮肿瘤。
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.
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影响因子：
23.4
作者：
Moch, Holger;Cubilla, Antonio L.;Ulbright, Thomas M.
通讯作者：
Ulbright, Thomas M.
影响因子：
2.4
作者：
Nishiyama, Naotaka;Kitamura, Hiroshi;Tsukamoto, Taiji
通讯作者：
Tsukamoto, Taiji
影响因子：
6.4
作者：
Nakashima, Masahiro;Suzuki, Keiji;Sekine, Ichiro
通讯作者：
Sekine, Ichiro
DOI：
10.1083/jcb.153.3.613
发表时间：
2001-04-30
期刊：
The Journal of cell biology
影响因子：
--
作者：
Rappold I;Iwabuchi K;Date T;Chen J
通讯作者：
Chen J
影响因子：
5
作者：
Alberg, Anthony J.;Kouzis, Anthony;Comstock, George W.
通讯作者：
Comstock, George W.