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 pote ncy of diverse cancers. In this prospective study, we clarified the impact of 53BP1 express ion via IF as a biomarker to differentiate thyroid follicular tumors (FTs) with liquid-bas ed 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 F T cases were collated with the type of 53BP1 immunoreactivity in LBC. The mean incidence e xpressing 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 8 9.3, 83.3, 71.4, and 94.3%, respectively. Therefore, IF analysis of 53BP1 expression can be employed as a novel technique to diagnose FTs and to distinguish between different t ypes of FTs using LBC.

Keywords

• 53bp1
• genomic instability
• immunofluorescence
• thyroid follicular tumor
• liquid-based cytology