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甲状腺乳头状癌特异性肿瘤标志物的临床应用
滕伟强,陈梦婕,韩换,高颖娜,张才云,郑宏良,朱乘婧*
0
(海军军医大学(第二军医大学)第一附属医院耳鼻咽喉头颈外科, 上海 200433
*通信作者)
摘要:
目的 探讨细胞角蛋白19(CK19)、半乳糖凝集素3(Gal-3)、p53、拓扑异构酶Ⅱ(TopoⅡ)、Ki-67、细胞周期蛋白D1(CCND1)、人骨髓内皮细胞标志物1(HBME-1)、B-Raf原癌基因丝氨酸/苏氨酸蛋白激酶V600E突变型(BRAFV600E)在甲状腺乳头状癌(PTC)病理诊断中的临床应用价值。方法 选取100例PTC和40例甲状腺良性病变标本,采用免疫组织化学染色EnVision法检测CK19、Gal-3、p53、TopoⅡ、Ki-67、CCND1和HBME-1在组织中的表达情况,通过荧光PCR检测BRAFV600E在组织中的表达情况。结果 PTC组织中CK19、Gal-3、TopoⅡ、CCND1、HBME-1和BRAFV600E阳性表达率[97.0%(97/100)、98.0%(98/100)、56.0%(56/100)、95.0%(95/100)、66.0%(66/100)、75.0%(75/100)]高于甲状腺良性组织[45.0%(18/40)、20.0%(8/40)、15.0%(6/40)、55.0%(22/40)、25.0%(10/40)、12.5%(5/40)],差异均有统计学意义(P均<0.01)。8种标志物单独用于PTC的诊断时,CK19、Gal-3的灵敏度最高(97.0%、98.0%),Gal-3的准确度最高(92.9%);3种标志物联合应用并以其中任意2种阳性作为阳性判断标准时,CK19、Gal-3、HBME-1组合检测PTC的准确度最高(96.4%),其次为BRAFV600E、CK19、Gal-3组合(91.4%)。结论 CK19、Gal-3、TopoⅡ、CCND1、HBME-1、BRAFV600E是诊断PTC的重要标志物,这些标志物联合应用有助于对形态不典型PTC与甲状腺良性病变进行鉴别。
关键词:  甲状腺乳头状癌  细胞角蛋白19  半乳糖凝集素3  B-Raf原癌基因丝氨酸/苏氨酸蛋白激酶  p53  拓扑异构酶Ⅱ  Ki-67  细胞周期蛋白D1  人骨髓内皮细胞标志物1
DOI:10.16781/j.CN31-2187/R.20220404
投稿时间:2022-05-11修订日期:2022-09-02
基金项目:国家自然科学基金(81970868,81972537,81200734).
Clinical application of specific tumor markers for papillary thyroid carcinoma
TENG Wei-qiang,CHEN Meng-jie,HAN Huan,GAO Ying-na,ZHANG Cai-yun,ZHENG Hong-liang,ZHU Cheng-jing*
(Department of Otorhinolaryngology Head and Neck Surgery, The First Affiliated Hospital of Naval Medical University (Second Military Medical University), Shanghai 200433, China
*Corresponding author)
Abstract:
Objective To investigate the clinical application of cytokeratin 19 (CK19), galectin-3 (Gal-3), p53, topoisomerase Ⅱ (TopoⅡ), Ki-67, cyclin D1 (CCND1), human bone marrow endothelial marker 1 (HBME-1), and B-Raf proto-oncogene, serine/threonine kinase V600E mutant type (BRAFV600E) in the pathological diagnosis of papillary thyroid carcinoma (PTC). Methods A total of 100 PTC and 40 benign thyroid lesions were selected. The expression of CK19, Gal-3, p53, TopoⅡ, Ki-67, CCND1 and HBME-1 in tissues was detected by immunohistochemistry EnVision method, and the expression of BRAFV600E was detected by fluorescence polymerase chain reaction. Results The positive expression rates of CK19, Gal-3, TopoⅡ, CCND1, HBME-1 and BRAFV600E in PTC tissues (97.0%[97/100], 98.0%[98/100], 56.0%[56/100], 95.0%[95/100], 66.0%[66/100] and 75.0%[75/100]) were significantly higher than those in benign thyroid tissues (45.0%[18/40], 20.0%[8/40], 15.0%[6/40], 55.0%[22/40], 25.0%[10/40] and 12.5%[5/40]), and the differences were statistically significant (all P<0.01). CK19 and Gal-3 had the highest sensitivity (97.0% and 98.0%, respectively) and Gal-3 had the highest accuracy (92.9%) when the 8 markers were used alone for the diagnosis of PTC. Taking any 2 being positive of a 3 combination as the positive criterion, the combined application of CK19, Gal-3 and HBME-1 as diagnostic criteria for PTC had the highest accuracy of 96.4%. The combication of BRAFV600E, CK19 and Gal-3 showed high accuracy as well (91.4%). Conclusion CK19, Gal-3, TopoⅡ, CCND1, HBME-1 and BRAFV600E are important markers for the diagnosis of PTC, and the combined application of these markers can help to distinguish the abnormal PTC from benign thyroid lesions.
Key words:  papillary thyroid carcinoma  cytokeratin 19  galectin-3  B-Raf proto-oncogene, serine/threonine kinase  p53  topoisomerase Ⅱ  Ki-67  cyclin D1  human bone marrow endothelial marker 1