53BP1 expression as a biomarker to differentiate thyroid follicular tumors

Abstract

We have previously reported that the expression of p53-binding protein 1 (53BP1) in nuclear foci (NF), a marker reflecting DNA damage response (DDR), detected using immunofluorescence (IF) is useful to estimate the malignant potency of diverse cancers. In this prospective study, we clarified the impact of 53BP1 expression via IF as a biomarker to differentiate thyroid follicular tumors (FTs) with liquid-based cytology (LBC). A total of 183 consecutively obtained-LBC samples, which were preoperatively suspected as FTs, were analyzed. Before histological diagnosis, the type of 53BP1 immunoreactivity in LBC was classified as follows: low DDR type, one or two NF; high DDR type, three or more NF; large foci type, larger than 1.0 μm; abnormal type, intense nuclear staining. Among the 183 cases, 136 cases were postoperatively diagnosed as FTs including adenomatous goiter (AG, n=30), follicular adenoma (FA, n=60), FT-uncertain malignant potency (FT-UMP, n=18), and follicular carcinoma (FC, n=28), and 47 cases were diagnosed as tumors other than FTs or technically inadequate materials. Total 136 FT cases were collated with the type of 53BP1 immunoreactivity in LBC. The mean incidence expressing abnormal 53BP1 expression was significantly higher in FC than FA (9.5% vs. 2.6%, p-value <0.001). When adopting 4.3% as a cut-off value to distinguish FC from FA, the sensitivity, specificity, positive predictive value, and negative predictive value were 89.3, 83.3, 71.4, and 94.3%, respectively. Therefore, IF analysis of 53BP1 expression can be employed as a novel technique to diagnosis FTs and distinguish between different types of FTs using LBC.

Identification of invasive subpopulations using spatial transcriptome analysis in thyroid follicular tumors

“…Several studies have proposed the use of various markers for distinguishing between follicular thyroid adenomas and carcinomas. Sato et al [ 5 ] reported the utility of p53-binding protein 1 (53BP1) expression in nuclear foci, a marker reflecting the DNA damage response, to distinguish follicular thyroid carcinomas from adenomas. 53BP1 showed high sensitivity (89.3%) and specificity (83.3%), although the interpretation of results required advanced techniques.…”

“…Many studies have reported methods to distinguish follicular thyroid adenomas from carcinomas [ 5 - 8 ]. Some of them require special equipment and techniques for analysis [ 5 , 6 ].…”

“…Many studies have reported methods to distinguish follicular thyroid adenomas from carcinomas [ 5 - 8 ]. Some of them require special equipment and techniques for analysis [ 5 , 6 ]. Markers used in immunohistochemistry may be helpful to distinguish between the two using simple methods.…”

Molecular Pathological Characteristics of Thyroid Follicular-Patterned Tumors Showing Nodule-in-Nodule Appearance with Poorly Differentiated Component

“…We previously reported that the number of 53BP1 nuclear foci increases with the malignant potential of TFTs, such as FA, MFC, and WFC [ 16 ]. Our recent study using liquid-based cytology samples obtained from resected TFTs suggested that the frequency of abnormal type 53BP1 expression in TFTs could be an attractive candidate biomarker for distinguishing FC from FA [ 27 ]. This study demonstrated that the frequency of abnormal type 53BP1 expression in NN with PDc was significantly higher than in benign nodules, but not in FCs, and that the incidence of NRAS codon 61 and TERT -p mutations in NN with PDc was comparable to that of FCs.…”

Evaluation of Trace Elements in Thyroid Adenomas Using Energy Dispersive X-Ray Fluorescent Analysis

“…However, because there is a 20% possibility of malignant transformation, TA should be differentiated from other thyroid nodular diseases such as nodular goiter (NG) and thyroid cancer (TC). The distinguishing between the TA and TC is tricky, therefore new differential diagnostics and TA biomarkers are needed [2,3].…”