甲状腺乳头状癌NIS蛋白表达对^(131)I疗效的预测及与BRAF基因突变的关系

The correlation between expression of NIS and BRAF mutation,clinicpathological parameters and results of ^(131)Ⅰ treatment in papillary thyroid cancer

目的:探讨甲状腺乳头状癌钠碘转运体(sodium/iodide symporter,NIS)蛋白表达对131I疗效的预测及与BRAF基因突变的关系。方法:收集甲状腺乳头状癌根治术后行131I治疗的患者60例,临床随访131I疗效分为完全缓解和不完全缓解,不完全缓解组再分为摄碘和不摄碘。免疫组化法对患者肿瘤原发灶NIS蛋白表达进行分析,根据表达强弱分为0,1,2,3分。应用Pyrosequencing焦磷酸测序技术对肿瘤原发灶BRAF基因突变进行分析。对131I疗效各组和BRAF突变两组的NIS蛋白表达水平进行统计分析。结果:甲状腺乳头状癌NIS蛋白染色阳性颗粒主要定位于细胞浆,阳性评分为1.45±0.77。131I治疗完全缓解患者29例,其NIS蛋白水平(1.62±0.86)与不完全缓解组(1.29±0.64)无统计学差异(P=0.100)。但对不完全缓解组进一步研究发现,不摄碘组NIS蛋白水平(1.00±0.60)显著低于摄碘组(1.47±0.61),P=0.043。伴BRAF基因突变患者检出47例(78.3%),其NIS蛋白评分(1.34±0.73)与携带野生型基因患者(1.85±0.80)比较差异有统计学意义,P=0.035。结论:131I疗效与肿瘤原发灶NIS蛋白表达水平没有明显关系,但不摄碘的持续不缓解患者常伴有肿瘤NIS蛋白表达降低和缺失;伴BRAF基因突变患者其NIS蛋白表达降低,分化程度更差。

Objective：To explore the correlation between expression of NIS and BRAF mutation, clinicpathological parameters and results of 1311 treatment in papillary thyroid cancer. Methods： All 60 papillary thyroid cancer patients undergoing surgery and 131^I treatment were reviewed and divided into complete remission group and incomplete remission group. Immunohistochemical analysis of NIS was performed, scored 0, 1, 2, 3 by intensity. And BRAF mutation was analyzed. Results： Staining of NIS was mostly at cytoplasm in papillary thyroid cancer, and scored 1.45 ± 0.77 on average. 48.3% （29/60）were observed as complete remission, and no differences were found between the two groups （P =0. 100）. However if the incomplete remission group was subdivided into radioiodine uptake and no uptake, the latter group was with lower NIS protein than the former group （ P = 0. 043 ）. BRAF mutation was confirmed in 78.3% （47/60） patients, and lower NIS protein level was found with BRAF mutation group, compared with wild type BRAF gene （P = 0. 035 ）. Conclusion：NIS protein level was not correlated the result of 131^I treatment in papillary thyroid cancer patients, but incurred patients with no 131^ I uptake always got a lower NIS protein level. Patients with BRAF mutation may have obviously lower NIS protein level.