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.
Typically, local spread and lymph-vascular space invasion (LVSI) occur before lymph node (LN) and distant metastases during the progression of uterine cervical cancer. The prognostic value of LVSI in cervical superficially invasive squamous cell carcinoma (SISCC) is still debated. We encountered a rare case of cervical SISCC without LVSI presenting with multiple LN metastases, including pelvic, para-aortic, and left supraclavicular LNs. Immunohistochemical analysis of p16INK4a and in situ hybridization of human papillomavirus confirmed the relationship of the cervical SISCC and pelvic LN metastases. Aspiration cytology of the left supraclavicular LN showed squamous cell carcinoma and our final diagnosis was uterine cervical squamous cell carcinoma, stage IVB. The patient underwent adjuvant chemotherapy. Although relapse was observed at the vaginal stump and in pelvic and para-aortic LNs, chemotherapy and radiotherapy were effective. The patient is alive without disease 40 mo after initial treatment. This is the first case report of cervical SISCC without LVSI presenting with supraclavicular LN metastasis, which contributes to our understanding of the value of LVSI. Immunohistochemical analysis of p16INK4a and in situ hybridization of human papillomavirus were useful in confirming the relationship of cervical SISCC and its metastases. As cervical SISCC with LN metastasis is rare, multi-institutional joint research is needed to clarify its prognosis and appropriate treatment.
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