中文摘要：

目的探讨甲状腺乳头状癌（PTC）中促甲状腺激素受体（TSHR）和钠/碘协同转运体（NIS）蛋白表达与相应基因的甲基化及T1799A BRAF基因突变的关系。方法应用直接测序法检测60例PTC和20例癌旁正常甲状腺组织中T1799A BRAF突变;甲基化特异性PCR（MSP）检测上述标本中的TSHR和NIS的基因甲基化;免疫组化法检测蛋白表达。结果60例PTC标本中,BRAF突变率为65%（n=39）,TSHR和NIS基因甲基化的发生率分别为43%（n=26）和27%（n=16）,突变和甲基化与临床病理特征未见显著关联。TSHR蛋白表达阳性评分在TSHR甲基化阳性组和阴性组中分别为1.3±0.5和1.7±0.7（P=0.009）,NIS蛋白表达阳性评分在NIS甲基化阳性组和阴性组中分别为1.1±0.5和1.5±0.6（P=0.019）。BRAF突变的PTC病例中,TSHR和NIS蛋白表达阳性评分显著低于野生组（TSHR,1.4±0.5 vs 1.8±0.8,P=0.031;NIS,1.3±0.6 vs 1.7±0.6,P=0.009）,TSHR和NIS基因甲基化发生率显著高于野生组（TSHR,54%vs 36%，P=0．049；NIS，24％vs10％，P=0．034）。结论PTC中相应基因的甲基化和BRAF突变可能是TSHR和NIS蛋白表达减弱并分布异常的原因。

英文摘要：

Objective To investigate the association of the expressions of thyroid stimulating hormone receptor （TSHR） and Na^＋/I^- symportor （NIS） with aberrant hypermethylation and T1799A BRAF mutation in papillary thyroid cancer （PTC）. Methods The T1799A BRAF mutation in 60 PTC samples and 20 normal thyroid tissue samples was determined by direct sequencing, and the promoter methylation status of TSHR and NIS genes was examined using methylation-specific PCR （MSP）. The expressions of TSHR and NIS proteins were detected by immunohistochemistry. Results T1799A BRAF mutation was found in 39 of 60 PTC samples （65%）. TSHR and NIS genes were hypermethylated in 26 （43%） and 16 （27%） of 60 PTC samples, respectively. Neither mcthylation nor BRAF mutation was associated with the clinieopathologieal features of FFC. TSHR immunostaining scores were 1.3±0.5 in methylation-positive group and 1.7±0.7 in methylation-negative group （P=0.009 ）, and were 1.4±0.5 in BRAF mutation-positive group and 1.8±0.8 in mutation-negative group （P =0.031 ）. NIS immunosraining scores were 1.1±0.5 in methylation-positive group and 1.5±0.6 in methylation-negative group （P =0.019）,and were 1.3±0.6 in BRAF mutation-positive group and 1.7±0.6 in mutation-negative group （P =0.009 ）. Methylation of TSHR and NIS genes were associated with the T1799A BRAF mutation in PTC [TSHR,21/39 （54%） for the mutated group vs 5/21 （24%） for the wild-type group,P =0.049; NIS, 14/39 （36%） for the mutated group vs 2/21 （ 10% ） for the wild-type group, P =0.0341. Conclusion Methylation of TSHR and NIS genes as well as the BRAF mutation seem to be the mechanism behind the decrease and dysfunction of TSHR and NIS proteins in PTC.