Dong Shuai, Xie Xiao-Jun, Xia Qing, Wu Yi-Jun
Thyroid Disease Diagnosis and Treatment Center, The First Affiliated Hospital, College of Medicine, Zhejiang University Hang Zhou 310003, China.
Department of Endocrine, Zhejiang Provincial People's Hospital Hang Zhou 310000, China.
Am J Cancer Res. 2019 Aug 1;9(8):1786-1795. eCollection 2019.
Currently, no definitive diagnostic tool is available to distinguish unifocal and multifocal papillary thyroid carcinoma (PTC). This study aims to identify potential diagnostic markers of multifocal PTC. In 471 Hashimoto's thyroiditis (HT) patients, the significant difference was revealed in anti-thyroid peroxidase antibody (TPOAb) concentration, the cytokeratin-19 (CK-19) expression, the occurrence of the B-Raf proto-oncogene serine/threonine kinase (BRAF) mutations and the rearrangement in transformation (RET)/PTC. The patients' samples were assayed for the expression of CK-19, cyclooxygenase-2 (COX-2), galectin-3, and the protein human bone marrow endothelial cell marker-1 (HBME-1) using immunohistochemistry. The BRAF gene mutation was detected using a sequencer. Differences were examined using the Kruskal-Wallis test and the Chi-squared and Fisher's exact tests. The results showed that the elevated CK-19 expression, and the presence of BRAF mutations and RET/PTC rearrangements were indicators of multifocal PTC in HT, suggesting the need for total bilateral thyroidectomy. Among HT patients with TPOAb > 1300 IU/Ml, the occurrence of central lymph node metastasis is significantly higher in multi-focal PTC than single-focal PTC. Therefore, these markers may prove useful for discerning between uni- and multifocal PTC, thereby preventing unnecessary surgery in the treatment of unifocal PTC and promoting sufficient treatment of multifocal PTC.
目前,尚无明确的诊断工具可用于区分单灶性和多灶性甲状腺乳头状癌(PTC)。本研究旨在识别多灶性PTC的潜在诊断标志物。在471例桥本甲状腺炎(HT)患者中,抗甲状腺过氧化物酶抗体(TPOAb)浓度、细胞角蛋白-19(CK-19)表达、B-Raf原癌基因丝氨酸/苏氨酸激酶(BRAF)突变的发生情况以及转染重排(RET)/PTC存在显著差异。使用免疫组织化学检测患者样本中CK-19、环氧合酶-2(COX-2)、半乳糖凝集素-3和人骨髓内皮细胞标志物-1(HBME-1)蛋白的表达。使用测序仪检测BRAF基因突变。使用Kruskal-Wallis检验、卡方检验和Fisher精确检验来检验差异。结果表明,CK-19表达升高、BRAF突变的存在以及RET/PTC重排是HT中多灶性PTC的指标,提示需要进行双侧甲状腺全切术。在TPOAb>1300 IU/Ml的HT患者中,多灶性PTC中央淋巴结转移的发生率显著高于单灶性PTC。因此,这些标志物可能有助于区分单灶性和多灶性PTC,从而避免在单灶性PTC治疗中进行不必要的手术,并促进对多灶性PTC的充分治疗。