促甲状腺素抗氧化传导通路与甲状腺乳头状癌侵袭力的关系

目的 探讨促甲状腺素受体(thyroid-stimulating hormone recepter,TSHR)、抗氧化酶1(pemxiredoxin 1,Prxl)、硫氧还蛋白1(thioredoxin1,Trx1)、缺氧诱导因子1(hypoxia inducible factor-1,HIF-1)α在甲状腺乳头状癌侵袭、转移中的作用.方法 选取2003至2007年于天津市肿瘤医院手术切除的34例典型甲状腺乳头状癌石蜡包埋标本、39例高细胞型甲状腺乳头状癌石蜡包埋标本,以癌旁正常甲状腺组织作对照,采用免疫组织化学SP法,检测TSHR、Prx1、Trx1、HIF-1α在甲状腺乳头状癌中的表达,并将检测结果结合患者的临床资料(性别、年龄、肿瘤大小、局部侵犯、颈淋巴转移、组织学亚型、T分期)等进行分析.结果 甲状腺乳头状癌中的Prx1、Trx1、HIF-1α的阳性表达率均高于癌旁正常甲状腺组织(χ2值分别为5.49、6.16、40.48,P值均<0.05).甲状腺乳头状癌中的TSHR的阳性表达率低于癌旁正常甲状腺组织(χ2=15.70,P<0.05),高细胞型甲状腺乳头状癌的TSHR的阳性表达率低于典型甲状腺乳头状癌(χ2=4.24,P<0.05).肿瘤侵犯甲状腺被膜外、有颈淋巴转移、高细胞型、T3-T4期甲状腺乳头状癌的Prx1、Try1、HIF-1α的阳性表达率更高,差异有统计学意义(P值均<0.05).甲状腺乳头状癌中Trx1与Prx1、Trx1与HIF-1α的阳性表达具有关联性(列联系数分别为0.664和0.652,P值均<0.05).结论 甲状腺乳头状癌中Prx1、Trx1和HIF-1α的高表达与肿瘤的侵袭和转移有关,TSH可能通过Prx1-Trx1-HIF-1信号传导通路促进甲状腺癌的发展.

Correlation between thyroid-stimulating hormone-peroxiredoxin1 signaling pathway and invasion of papillary thyroid carcinoma

Objective In order to assess the significance of thyroid-stimulating hormone receipt (TSHR), perexiredexin1 (Prx1), thioredoxinl (Trx1), hypoxia inducible factor-1 (HIF-1) α in invasion and metastasis of papillary thyroid carcinoma(PTC). Methods The 34 paraffin-embedded specimen of classical PTC,39 of tall cell variant of FIG and normal thyroid tissues adjacent to cancer operated in Tianjin Cancer Hospital from 2003 to 2007 were tested. The expressions of TSHR, Prx1,Trx1, HIF-1 α in the specimen were assayed by immunohistochemical staining. The correlation between the 4 factors (TSHR, Prx1, Trx1,HIF-1α) and clinical features of FIG such as gender, age, tumor size, invasion, lymph node metastasis, histological type and T stage were studied. Results The rates of immuno-positive staining Prx1,Trx1 and HIF-1α in PTC were higher than the normal thyroid tissues adjacent to cancer with significant difference respectively(χ2 were 5.49, 6. 16 and 40. 48, P <0.05). The positive expression rate of TSHR in PTC was lower than the normal thyroid tissues adjacent to cancer(χ2=15.70, P<0.05), in tall cell variant of PTC was lower than classical PTC(χ2=4. 24,P <0.05). The positive expression rates of Prx1,Trx1 and HW-1α in PTC with local invasion, with lymph node metastasis, in tall cell variant and in stage T3-T4 were higher than PTC without local invasion, without metatasis, in classical variant and in stage T1-T2 with significant difference respectively(P<0.05). There were correlation between the expressions of Prx1 and Trx1,Trx1 and HIF-1α (r, were 0. 664 and 0. 652, P <0.05). Conclusions The high expressions of Prx1,Trx1 and HIF-1α were related to invasion and lymph node metastasis in PTC. TSH may promote the development of thyroid carcinoma by TSH-Prx1-Trx1-HIF-1 signaling pathway.