Sato Ayako, Matsuda Katsuya, Motoyama Takahiro, Mussazhanova Zhanna, Otsubo Ryota, Kondo Hisayoshi, Akazawa Yuko, Higuchi Miyoko, Suzuki Ayana, Hirokawa Mitsuyoshi, Miyauchi Akira, Nagayasu Takeshi, Nakashima Masahiro
Department of Surgical Oncology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
Department of Tumor and Diagnostic Pathology, Atomic Bomb Disease Institute, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
Endocr Connect. 2021 Mar;10(3):309-315. doi: 10.1530/EC-20-0630.
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 diagnose FTs and to distinguish between different types of FTs using LBC.
我们之前曾报道，利用免疫荧光法（IF）检测到的核灶（NF）中p53结合蛋白1（53BP1）的表达，这一反映DNA损伤反应（DDR）的标志物，有助于评估多种癌症的恶性潜能。在这项前瞻性研究中，我们阐明了通过IF检测53BP1表达作为生物标志物对甲状腺滤泡性肿瘤（FTs）进行液基细胞学（LBC）鉴别诊断的影响。共分析了183例术前疑似为FTs的连续获取的LBC样本。在组织学诊断之前，LBC中53BP1免疫反应性的类型分类如下：低DDR型，一个或两个NF；高DDR型，三个或更多NF；大灶型，大于1.0μm；异常型，强烈的核染色。在这183例病例中，136例术后诊断为FTs，包括腺瘤性甲状腺肿（AG，n = 30）、滤泡性腺瘤（FA，n = 60）、恶性潜能不确定的FT（FT-UMP，n = 18）和滤泡癌（FC，n = 28），47例诊断为非FTs肿瘤或技术上不合格的材料。将136例FT病例与LBC中53BP1免疫反应性类型进行对照。FC中53BP1异常表达的平均发生率显著高于FA（9.5%对2.6%，P值<0.001）。当采用4.3%作为区分FC和FA的临界值时，敏感性、特异性、阳性预测值和阴性预测值分别为89.3%、83.3%、71.4%和94.3%。因此，对53BP1表达进行IF分析可作为一种新技术，用于诊断FTs并利用LBC区分不同类型的FTs。
