Background/Aim: P53-binding protein 1 (53BP1) is one of the DNA damage response (DDR) molecules. This study aimed to assess 53BP1 expression by immunofluorescence (IF) as a biomarker to differentiate between oral squamous epithelial lesions (OSELs). Materials and Methods: We analyzed 129 archival oral biopsy samples, including 18 benign squamous lesions (BSLs), 37 low-grade dysplasias (LGDs), 22 high-grade dysplasias (HGDs), and 52 oral squamous cell carcinomas (OSCCs). 53BP1 and Ki-67 expressions were examined by double IF to assess the type of 53BP1 expression. Results: We found that OSCC exhibited several 53BP1 nuclear foci, particularly high-DNA damage response (HDDR) and large focus (LF)-type, suggesting the presence of endogenous DNA double-strand breaks in the cancer genome, which could disrupt DDR and induce genomic injury. We also found a difference in 53BP1 expression between LGD and HGD, but not between BSL and LGD. Among the Ki-67-positive cells, HDDRand LF-type expressions were higher in OSELs of higher grades. Conclusion: 53BP1 expression can be a valuable biomarker for OSELs to help estimate the grade of oral epithelial dysplasia.Oral squamous cell carcinoma (OSCC) incidence is estimated to be more than 500,000 annually (1). It is commonly preceded by oral epithelial dysplasia (OED), and its 5-year survival rate can be improved by early-stage diagnosis (2). The 4 th edition of the WHO Classification of Head and Neck Tumours (2017) defines OED as 'a spectrum of architectural and cytological epithelial changes caused by accumulation of genetic changes associated with an increased risk of progression to squamous cell carcinoma (SCC) (3). However, dysplasia grading is poorly reproducible between pathologists. Although OED is traditionally divided into three severity grades, a binary system is also advocated to improve reproducibility. Consensus grading after reviewing by multiple pathologists may enhance diagnostic reliability. The Japanese Society of Oral Oncology recommends a binary system, such as lowgrade and high-grade dysplasia (LGD and HGD), to diagnose OED based on clinical management (4). HGD may include carcinoma in situ, and commonly develop into SCC, hence HGD lesions are usually recommended for active surgical intervention (5). Most LGDs never progress to carcinoma, so a 'wait and see' policy may be adopted for these lesions. Thus, the clinical management of OED is dependent on the histopathological diagnosis by biopsy.Histological findings of architectural and cytological disturbances in biopsy specimens are critical for OED diagnosis. However, there is lack of consistent evidence to indicate translation of individual features into a dysplasia grade. Thus, the issue of poor consensus is based on the current diagnostic criteria underlying the low reproducibility of OED differential diagnosis and necessitates establishment of an ancillary technique to diagnose OED. P53-binding protein 1 (53BP1) is a DNA damage response (DDR) molecule with a BRCA1 C-terminal domain (6). 53BP1 4771 This a...
Thyroid follicular-patterned tumors (TFTs) showing nodule-in-nodule (NN) appearance with poorly differentiated component (PDc) but neither invasion nor metastasis are diagnosed as benign nodules. Although PDc exhibits histologically aggressive features relative to the outer nodule (Out-N), its pathological significance remains unclear. TP53 binding protein-1 (53BP1) is a DNA damage response (DDR) molecule that rapidly localizes at DNA double-strand breaks. Using dual-color immunofluorescence with Ki-67, the profile of 53BP1 expression is shown to be significantly altered during diverse tumorigenesis. In this study, we aimed to elucidate the malignant potential of PDc at the molecular level. We analyzed the profile of 53BP1 expression and NRAS codon 61 and TERT-promoter (TERT-p) mutations in 16 cases of TFTs showing NN with PDc compared to 30 adenomatous goiters, 31 follicular adenomas, 15 minimally invasive follicular carcinomas (FCs), and 11 widely invasive FC cases. Our results revealed that the expression level of abnormal type 53BP1 and incidence of NRAS and TERT-p mutations in PDc were comparable to FCs, suggesting a malignant potential. Because co-expression of 53BP1 and Ki-67 can be an indicator of altered DDR, the development of PDc in NN may be associated with DDR impairments after harboring NRAS and TERT-p mutations.
Nodal metastasis is crucial for determining the stage of well-differentiated thyroid cancer (WTC) in patients older than 55. Well-formed thyroid follicular inclusions (TFIs) are occasionally encountered in the cervical lymph nodes (LNs) of patients with papillary thyroid carcinoma (PTC), and it is difficult to determine whether they are true nodal metastases or ectopic thyroid tissues (ETT). This study aimed to elucidate the impact of the expression of the DNA damage response molecule TP53-binding protein 1 (53BP1) using immunofluorescence (IF) as a biomarker to differentiate TFIs in cervical LN by comparing the mutation analyses of primary thyroid cancers. The data demonstrated the necessity for the differential diagnosis of true metastases from ETT among TFIs in cervical LNs. PTC-like nuclear features using hematoxylin–eosin staining combined with immunohistochemistry for conventional biomarkers of PTC, including BRAFV600E protein, were most helpful in identifying metastatic follicular-patterned carcinomas. In conclusion, IF analysis of 53BP1 expression could be an excellent ancillary technique to distinguish metastatic carcinoma or ETT from TFIs in LNs, particularly in cases other than BRAFV600E-mutated PTC.
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