甲状腺乳头状癌特异性肿瘤标志物的临床应用  

Clinical application of specific tumor markers for papillary thyroid carcinoma

作　　者：滕伟强 陈梦婕[1] 韩换 高颖娜[1] 张才云[1] 郑宏良[1] 朱乘婧 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)

机构地区：[1]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

出　　处：《海军军医大学学报》2022年第10期1206-1210,共5页Academic Journal of Naval Medical University

基　　金：国家自然科学基金(81970868,81972537,81200734)。

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(BRAF^(V600E))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BRAF^(V600E)在组织中的表达情况。结果PTC组织中CK19、Gal-3、TopoⅡ、CCND1、HBME-1和BRAF^(V600E)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BRAF^(V600E)、CK19、Gal-3组合(91.4%)。结论CK19、Gal-3、TopoⅡ、CCND1、HBME-1、BRAF^(V600E)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。Objective To investigate the clinical application of cytokeratin 19(CK19),galectin-3(Gal-3),p53,topoisomeraseⅡ(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(BRAF^(V600E))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 BRAF^(V600E) was detected by fluorescence polymerase chain reaction.Results The positive expression rates of CK19,Gal-3,TopoⅡ,CCND1,HBME-1 and BRAF^(V600E) 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 BRAF^(V600E),CK19 and Gal-3 showed high accuracy as well(91.4%).Conclusion CK19,Gal-3,TopoⅡ,CCND1,HBME-1 and BRAF^(V600E) 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.

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 

分 类 号：R736.1[医药卫生—肿瘤]