甲状腺乳头状癌BRAFV600E基因突变与远处转移灶摄碘能力的相关性研究

Relationship between BRAFv600E mutation and radioactive iodine uptake in distant metastases from papillary thyroid cancer

目的 探讨甲状腺乳头状癌（PTC）原发灶V-raf鼠肉瘤滤过性病毒致癌基因同源体B1 （BRAF） v600E基因突变与PTC远处转移病灶摄碘能力间的关系.方法 选取2011年1月至2012年12月收治的PTC伴远处转移患者40例（男21例,女19例,平均发病年龄39.8岁）,按其原发灶BRAFv600E基因是否突变分为突变组和野生组,比较2组患者临床、病理、血清学特征的差异,探讨BRAFV00E基因突变与远处转移灶摄碘的关系;分析BRAFve0E基因突变与治疗后Tg变化趋势的关系.采用两样本t检验、x2检验或Fisher确切概率法分析数据.结果 转移性PTC患者BRAFv600E基因突变率为30.0％（12/40）,突变组（n=12）与野生组（n=28）患者临床、病理、血清学特征差异均无统计学意义（t=-0.533～1.728,x2=-1.951 ～1.088,均P＞0.05）.40例患者中,12例患者远处转移灶不摄碘,突变组与野生组中不摄碘的发生率分别为83.3％（10/12）和7.1％（2/28）,差异有统计学意义（x2=19.734,P＜0.05）,提示BRAFv600E突变组较野生组远处转移灶更易出现不摄碘.野生组66.7％（14/21）的患者131I治疗后Tg呈下降趋势,19.0％ （4/21） Tg稳定无明显变化,14.3％（3/21） Tg逐渐增高.突变组中所有患者131I治疗后Tg无下降趋势,2/9呈升高趋势,7/9保持稳定并且转移灶无碘摄取.结论 伴有BRAFv600E基因突变的PTC患者远处转移灶摄碘能力下降,对131I治疗反应差;BRAFv600E基因突变的检测可能有助于对伴有远处转移的PTC 131I治疗适应证的选择及其疗效预测.

Objective To investigate the relationship between V-raf murine sarcoma viral oncogene homolog B1 （BRAF）v600E mutation and radioactive iodine （RAI） uptake in distant metastases from papillary thyroid cancer（PTC）.Methods From January 2011 to December 2012,40 PTC patients （21 males,19 females,average age 39.8 years） with distant metastases were recruited and divided into mutation group and wild group according to the BRAFv600E mutation in primary lesions.The clinical,pathological and serological differences were compared between the two groups.The relationship between BRAFv600E mutation and RAI uptake capability in distant metastases from PTC,as well as its relationship with Tg change after 131I treatment were investigated.Statistical analysis was performed with two-sample t test,x2 test or Fisher exact test.Results The BRAFv600E mutation rate was 30.0％ （12/40） in patients with metastases from PTC.There was no significant difference in clinical,pathological and serological features between mutation group （n =12） and wild group （n=28; t：from-0.533 to 1.728,x2：from-1.951 to 1.088,all P＞0.05）.Twelve PTC patients had no RAI uptake in the distant metastases,of which 10 belonged to mutation group （83.3％,10/12） and 2 belonged to wild group （7.1％,2/28; x2=19.734,P＜0.05）.BRAFv600E mutation group was more likely to have no RAI uptake in the distant metastases.Tg change after 131I treatment in 30 patients were analyzed.In the wild group,Tg level decreased in 66.7％ （14/21） patients,stabilized in 19.0％ （4/21）and increased in 14.3％ （3/21）patients.While there was no decrease of Tg in the mutation group （0/9）.Two patients had increased Tg level and 7 patients （with no RAI uptake） kept stable in mutation group.Conclusions Due to poor RAI uptake capability in PTC patients with BRAFv600E mutation,both primary and metastatic sites may have poor response to 131I treatment.Molecular detection of BRAFv600E mutation might be helpful for choosing PTC with distant metastases and predicting the effect of 131 I treatment.