TRβ1、β-catenin及CyclinA2在甲状腺乳头状癌的表达及临床意义

Expressions and Clinical Significance of TRβ1,β-catenin and Cyclin A2 in Papillary Thyroid Carcinoma

目的探讨甲状腺激素受体β1(thyroid hormone receptorβ1,TRβ1)、β-链蛋白(β-catenin)及细胞周期蛋白A2(Cyclin A2)在甲状腺乳头状癌(thyroid papillary carcinoma,TPC)组织中的表达及意义。方法应用免疫组化(SP)法分别检测30例正常甲状腺组织、30例结节性甲状腺肿伴乳头状增生(nodular goiter with papillary hyperplasia,NGWPH)及116例TPC组织中TRβ1、β-catenin及Cyclin A2的表达,同时检测肿瘤淋巴管密度(lymphtic vessel density,LVD),分析它们与临床病理指标的关系。结果与正常甲状腺组织和NGWPH组织比较,TPC组织中TRβ1的表达阳性率降低,β-catenin在细胞膜表达显著减弱,而胞质表达明显增强,Cyclin A2的表达阳性率升高,差异有统计学意义(P<0.01)。相关性分析结果显示,TRβ1与β-catenin和Cyclin A2的表达呈负相关(r=-0.656和-0.525,均P<0.01),β-catenin和Cyclin A2呈正相关(r=0.384,P<0.01);淋巴结转移组的LVD显著高于无淋巴结转移组(P<0.05);TRβ1低表达、β-catenin胞质异常表达及Cyclin A2过表达与TPC包膜外侵、LVD及淋巴结转移有关(P<0.05),而与患者年龄、性别、组织类型、肿瘤直径、是否为多病灶无相关性(P>0.05)。结论 TRβ1通过使β-catenin在细胞内大量蓄积,继而诱导下游靶基因Cyclin A2表达途径参与TPC的发生和进展。

Objective To explore the expression and clinical significance of TRβ1,β-catenin and Cyclin A2 in PTC. Methods Immunohistochemical SP method was used to detect the expression of TRβ1, β-catenin and Cyclin A2 in 30 cases of normal thyroid tissue, 30 cases of nodular goiter with papillary hyperplasia （NGWPH） and 116 cases of human PTC specimen, respectively. lymphtic vessel density （LVD） inside the PTC was also determined, and analysed the correlation with clinical indicators. Results Compared with normal thyroid tissue and NGWPH tissues group, The positive expression rate of TRβ1 decreased and Cyclin A2 increased in TPC group, β-catenin expression in the membrane decreased and expression in the cytoplasm enhanced obviously. The difference was statistically significant （P〈0.01）. Correlation analysis showed that the TRβ1 and β-catenin were negative correlation with the expression of Cyclin A2 （r=-0.656 and-0.525, Both P〈0.01）, while, β-catenin and Cyclin A2 were positively correlated （r=0.384, P〈0.01）. LVD of lymphnode metastasis group was significantly higher than without lymphnode metastasis （P〈0.05）. Low expression of TRβ1, overexpression of Cyclin A2 and abnormal expression of β-catenin in cytoplasm were related to extracapsular spread, LVD and lymphnode metastasis in TPC （P〈0.05）, but not related to the patients＇ age, gender, histological type, tumor diameter, whether multifocal （P〉0.05）. Conclusion TRβ1 probablely involved in thyroid carcinoma＇s occurrence and aggression through making β-catenin accumulate in intracellular, which up-regulated the downstream target genes expression of Cyclin A2.