Significance of p53-Binding Protein 1 Nuclear Foci in Cervical Squamous Intraepithelial Lesions: Association With High-Risk Human Papillomavirus Infection and P16INK4a Expression
Significance of p53-Binding Protein 1 Nuclear Foci in Cervical Squamous Intraepithelial Lesions: Association With High-Risk Human Papillomavirus Infection and P16INK4a Expression
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DOI：
10.1177/1073274819901170
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发表时间：
2020-01-01
期刊：
影响因子：
2.6
通讯作者：
Masuzaki, Hideaki
中科院分区：
文献类型：
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作者：
Kawashita, Sayaka;Matsuda, Katsuya;Masuzaki, Hideaki
由于p53结合蛋白1 （53BP1）定位于DNA双链断裂位点并迅速形成核病灶（NF），其存在可能是内源性基因组不稳定性（GIN）的一个指标。我们之前的研究表明，宫颈细胞中的53BP1 NF随着肿瘤的进展而增加，这表明53BP1的表达对于宫颈癌发生过程中恶性潜能的估计具有重要意义。本研究旨在进一步阐明53BP1表达作为宫颈鳞状上皮内病变（SIL）的生物标志物的影响。采用高危人乳头瘤病毒（HR-HPV）阳性患者的81份组织样本，包括17份正常宫颈上皮，22份宫颈上皮内瘤变（CIN） 1, 21份CIN2, 21份CIN3，用于53BP1和Ki-67/p16（INK4a）表达的双标记免疫荧光和HR-HPV原位杂交。我们分析了53BP1表达类型与CIN分级、HR-HPV感染状态、p16（INK4a）表达和CIN预后等参数之间的关系。53BP1的表达类型与CIN的组织学分级和HR-HPV原位杂交信号模式显著相关（P < 0.0001）。53BP1与p16（INK4a）表达水平有显著相关性（r = 0.73, P < 0.0001）。53BP1表达类型与CIN预后无相关性。我们认为53BP1表达类型是SIL的一个有价值的生物标志物，它可以帮助估计反映HR-HPV与宿主基因组整合引起的复制应激的宫颈病变的等级和GIN。
As p53-binding protein 1 (53BP1) localizes to the sites of DNA double-strand breaks and rapidly forms nuclear foci (NF), and its presence may be an indicator of endogenous genomic instability (GIN). We previously showed that 53BP1 NF in cervical cells increase with neoplastic progression, indicating the significance of 53BP1 expression for the estimation of malignant potential during cervical carcinogenesis. This study aimed to further elucidate the impact of 53BP1 expression as a biomarker for cervical squamous intraepithelial lesion (SIL). A total of 81 tissue samples, including 17 of normal cervical epithelium, 22 of cervical intraepithelial neoplasia (CIN) 1, 21 of CIN2, and 21 of CIN3, from patients positive for high-risk human papillomavirus (HR-HPV) were used for double-label immunofluorescence of 53BP1 and Ki-67/p16(INK4a) expression and HR-HPV in situ hybridization. We analyzed associations between 53BP1 expression type with parameters such as CIN grade, HR-HPV infection status, p16(INK4a) expression, and CIN prognosis. Expression type of 53BP1 was significantly associated with histological grade of CIN and HR-HPV in situ hybridization signal pattern (P < .0001). There was a significant correlation between 53BP1 and p16(INK4a) expression levels (r = .73, P < .0001). However, there was no association between 53BP1 expression type and CIN prognosis. We propose that 53BP1 expression type is a valuable biomarker for SIL, which can help estimate the grade and GIN of cervical lesions reflecting replication stress caused by the integration of HR-HPV to the host genome.