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文章:

P53结合蛋白1作为下咽鳞状细胞肿瘤新型分子组织学标志物的意义

Significance of P53-Binding Protein 1 as a Novel Molecular Histological Marker for Hypopharyngeal Squamous Neoplasms

原文发布日期:28 August 2024

DOI: 10.3390/cancers16172987

类型: Article

开放获取: 是

 

英文摘要:

The DNA damage response protein p53-binding protein 1 (53BP1) accumulates and forms foci at double-strand DNA breaks, indicating the extent of DNA instability. However, the potential role of 53BP1 as a molecular biomarker for hypopharyngeal squamous cell carcinoma (HPSCC) diagnosis remains unknown. Here, we evaluated the potential of immunofluorescence-based analysis of 53BP1 expression to differentiate the histology of hypopharyngeal neoplasms. A total of 125 lesions from 39 surgically or endoscopically resected specimens from patients with HPSCC was histologically evaluated. 53BP1 expression in the nucleus was examined using immunofluorescence. The number of 53BP1 nuclear foci increased with the progression from non-tumorous to low-grade dysplasia, high-grade dysplasia, and squamous cell carcinoma. Unstable 53BP1 expression served as an independent factor for distinguishing lesions that required intervention. Colocalization of 53BP1 foci in proliferating cells, as assessed by Ki67, was increased in tumors ≥ 1000 µm in depth compared to those <1000 µm in depth at the tumor surface. Hence, the expression patterns of nuclear 53BP1 foci were associated with the progression of hypopharyngeal neoplasms. These findings suggest that 53BP1 could serve as an ancillary marker to support histological diagnosis and predict the factors that influence prognosis in patients with HPSCC.

 

摘要翻译: 

DNA损伤应答蛋白p53结合蛋白1(53BP1)在双链DNA断裂处聚集并形成灶点,指示DNA不稳定的程度。然而,53BP1作为下咽鳞状细胞癌(HPSCC)诊断分子生物标志物的潜在作用尚不明确。本研究评估了基于免疫荧光的53BP1表达分析在区分下咽肿瘤组织学类型方面的潜力。对39例HPSCC患者手术或内镜切除标本中的125个病变进行了组织学评估,并采用免疫荧光检测细胞核内53BP1的表达。结果显示,从非肿瘤组织到低级别不典型增生、高级别不典型增生直至鳞状细胞癌,53BP1核灶数量随病变进展而增加。不稳定的53BP1表达可作为区分需要干预性治疗的病变的独立因素。通过Ki67评估发现,在肿瘤表面深度≥1000 µm的肿瘤中,增殖细胞内53BP1灶点的共定位较深度<1000 µm的肿瘤更为显著。因此,核内53BP1灶点的表达模式与下咽肿瘤的进展相关。这些发现表明,53BP1可作为辅助标志物,支持HPSCC的组织学诊断并预测影响患者预后的因素。

 

原文链接:

Significance of P53-Binding Protein 1 as a Novel Molecular Histological Marker for Hypopharyngeal Squamous Neoplasms

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