Significance of p53-Binding Protein 1 Nuclear Foci in Cervical Squamous Intraepithelial Lesions: Association With High-Risk Human Papillomavirus Infection and P16INK4a Expression

• Published in: Cancer control Vol. 27; no. 1
• Main Authors: Kawashita, Sayaka, Matsuda, Katsuya, Kondo, Hisayoshi, Kitajima, Yuriko, Hasegawa, Yuri, Shimada, Takako, Kitajima, Michio, Miura, Kiyonori, Nakashima, Masahiro, Masuzaki, Hideaki
• Format: Journal Article
• Language: English
• Published: Los Angeles, CA SAGE Publications 20.02.2020; Sage Publications Ltd
• Subjects: Biomarkers; Carcinogenesis; Cervical cancer; Cervix; DNA damage; Epithelium; Genomes; Genomic instability; Human papillomavirus; Hybridization; Immunofluorescence; INK4a protein; Lesions; p16 Protein; p53 Protein; Prognosis; cervical squamous intraepithelial lesion; genomic instability; high-risk human papillomavirus; p16INK4a; 53BP1
• ISSN: 1073-2748; 1526-2359
• DOI: 10.1177/1073274819901170

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/p16INK4a expression and HR-HPV in situ hybridization. We analyzed associations between 53BP1 expression type with parameters such as CIN grade, HR-HPV infection status, p16INK4a 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 p16INK4a 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.