NIS和TSHR在分化型甲状腺癌中的表达及其与BRAF V600E突变的关系研究

目的探讨钠碘同向转运体(NIS)和促甲状腺激素受体(TSHR)在分化型甲状腺癌(DTC)组织中的表达及其与BRAF V600E突变的关系。方法采用免疫组织化SP法检测229例DTC、52例结节性甲状腺肿及31例正常甲状腺组织的NIS、TSHR表达情况,PCR直接测序法检测BRAF V600E突变,分析DTC组织NIS、TSHR表达情况与临床病理参数(性别、年龄、肿块大小、淋巴结转移、TNM分期及复发危险度分层)和BRAF V600E突变的关系。结果 NIS在DTC中的阳性率为55.5%(127/229),低于结节性甲状腺肿的78.9%(41/52)及正常甲状腺组织的77.4%(24/31),差异有统计学意义(P<0.05),且NIS表达与DTC的性别、年龄、肿块大小、淋巴结转移、TNM分期及复发危险度分层均无关。TSHR在DTC、结节性甲状腺肿及正常甲状腺组织的阳性率分别为41.0%(94/229)、48.1%(25/52)和45.2%(14/31),差异无统计学意义(P>0.05);TSHR表达与DTC的性别、年龄、淋巴结转移、TNM分期及复发危险度分层均无关,仅与肿块大小有关(P=0.029);NIS阳性率与BRAF V600E突变无关,但NIS细胞浆阳性表达中,BRAF V600E突变型比例(48.2%)高于BRAF V600E野生型比例(29.5%);NIS细胞膜阳性表达中,BRAF V600E突变型比例(51.8%)低于BRAF V600E野生型比例(70.5%),差异有统计学意义(P<0.05)。TSHR阳性率在BRAF V600E突变型中为47.9%,高于BRAF V600E野生型的28.7%,差异有统计学意义(P<0.05),而TSHR细胞浆和膜阳性表达与BRAF V600E突变无关。结论 DTC中NIS表达降低且定位与BRAF V600E突变有关,但BRAF V600E突变并不会影响TSHR定位;BRAF V600E突变型中TSHR表达增加,其具体机制还需进一步研究。

Expressions of NIS and TSHR in differentiated thyroid carcinoma and their association with BRAF V600E mutation

Objective To investigate the expressions of sodium iodide symporter ( NIS) and thyroid stimulating hormone re-ceptor ( TSHR) in differentiated thyroid carcinoma ( DTC) and their association with BRAF V600E mutation. Methods The immuno-histochemistry SP method was used to detect the expressions of NIS and TSHR in 229 cases of DTC, 52 cases of nodular goiter and 31 cases of normal thyroid tissues. The PCR direct sequencing was applied to detect the BRAF V600E mutations. The relationship between the expressions of NIS and TSHR in DTC tissues and the clinicopathological parameters ( gender, age, tumor size, lymph node metasta-sis, TNM stage and recurrence risk stratification) and BRAF V600E mutation were analyzed. Results The positive rate of NIS in DTC was 55. 5% (127/229), lower than 78. 9% (41/52) of nodular goiter and 77. 4% (24/31) of normal thyroid tissues with statistical significant difference( P<0. 05) . NIS expressions were not associated with gender, age, tumor size, lymph node metastasis, TNM stag-ing and recurrence risk stratification. The positive rates of DTC, nodular goiter and normal thyroid tissues were 41. 0% (94/229), 48. 1% ( 25/52) and 45. 2% ( 14/31) , and no significant difference was observed. TSHR expressions were not associated with gender, age, lymph node metastasis, TNM staging and recurrence risk stratification, but related with tumor size ( P=0. 029) . The positive ex-pression rate of NIS was not related to the mutation of BRAF V600E. However, as for the NIS expression in cell cytoplasm, BRAF V600E mutation type ( 48. 2%) was higher than BRAF V600E wild type ( 29. 5%) . In BRAF V600E mutation type, the expression rate of NIS in cell membrane was 51. 8%, lower than 70. 5% of BRAF V600E wild type (P<0. 05). The positive rate of TSHR in BRAF V600E mutations type was 47. 9%, higher than 28. 7% of BRAF V600E wild type, and the difference was statistical significant. TSHR expression in cytoplasm/ormembrane was not associated with BRAF V600E mutations. Conclusion The NIS expression was de-creased and the location of NIS expression may be associated with BRAF V600E mutations in DTC, but the location of TSHR expres-sion was not associated with BRAF V600E mutations. The specific mechanisms of the increased TSHR expression in patients with BRAF V600E mutations need further study.