多灶性甲状腺乳头状癌BRAF^(v600E)基因突变及临床生物学特性分析

BRAF^(v600E)Mutational Status and Ciinico-biological Characteristics of Multifocal Papillary Thyroid Carcinomas

目的:探讨多灶性甲状腺乳头状癌不同病灶的BRAF^(v600E)基因突变情况及其临床生物学特性。方法:对86例多灶性与282例单发病灶的甲状腺乳头状癌进行对比,研究其临床生物学特征,并对病灶进行BRAF^(v600E)突变检测分析。结果:86例多灶性甲状腺乳头状癌中,单侧病灶12例,双侧病灶74例;颈部淋巴结转移51例(59.3%);合并微小癌者46例(53.5%);合并桥本氏甲状腺炎者23例(26.7%);局部侵犯10例(11.6%);发生远处转移者1例(1.2%);10年生存率91.9%。41.9%的患者所有病灶均有BRAF^(v600E)突变,17.5%均不存在BRAF^(c600E)突变,至少有40.6%的多灶性甲状腺乳头状癌是独立起源的。结论:多灶性甲状腺乳头状癌多发生于双侧甲状腺,合并微小癌及桥本氏甲状腺炎者较多,颈部淋巴结转移及局部侵犯也较多,但远处转移率及10年生存率与单发的甲状腺乳头状癌比较无明显差异,BRAF^(600发E)突变可以间接预测不同病灶的起源问题,且有相当部分多灶性甲状腺乳头状癌的不同病灶是独立起源的。

Objective： To investigate the biological characteristics and management of papillary thyroid carcinomas （ PTCs ） and examine the BRAF^v600E mutational status of individual tumor loci to determine whether multifocal PTCs arise from the intrathyroidal spread of a single carcinoma or from independent primary tumors. Methods： A retrospective analysis of 86 patients with pathologically confirmed progressive multifocal PTC and who underwent surgery was performed. Analysis results were compared with 282 cases of solitary lesions of PTC to determine the clinical biological characteristics of multifocal PTCs. The BRAF^v600E mutational status of lesions was also analyzed. Results： Lymph node metastasis and vascular invasion occurred more frequently in multifocal PTCs than in solitary PTCs. No obvious differences between number of foci in LN-metastasis, extrathyroidal invasion, history of radiation, and microcarcinoma were observed among all the tumors studied. As well, no difference was observed between the distant metastasis and 10-year survival rates of solitary PTCs and multifocal PTCs. The heterogeneous distribution of BRAF mutations suggests that discrete tumor foci in multifocal PTCs occur as independent tumors. Conclusion： PTCs often present as multifocal tumors, which are associated with elevated risks of lymph node and distant metastases. The BRAF^v600E mutational status of multifocal PTCs must be considered in the design of targeted therapeutic approaches using BRAF pathway inhibitors.