甲状腺乳头状癌中BRAF基因的表达及意义

Expression of BRAF gene and its significance in papillary thyroid carcinoma

目的探讨BRAF基因突变与甲状腺乳头状癌(papillary thyroid carcinoma,PTC)及其临床病理特征之间的关系。方法采用免疫组化EnVision两步法、巢式PCR和基因测序法检测107例甲状腺石蜡包埋组织中BRAF点突变情况(包括93例PTC、5例滤泡癌、1例髓样癌、8例甲状腺腺瘤)。结果 93例PTC中,BRAF蛋白阳性者69例,阳性率为74.2%(69/93),BRAF蛋白对照组中仅有1例滤泡癌阳性表达(20%),而8例甲状腺腺瘤和1例髓样癌中BRAF蛋白均阴性表达。在PTC中检测到BRAF基因突变,突变率为32.3%(30/93),在其它类型的甲状腺病变中均未检测到BRAF基因突变。93例PTC的临床病理资料与BRAF蛋白表达及基因突变的对比分析显示,45岁以下患者的BRAF基因突变率高于45岁以上者,肿瘤直径>1 cm的患者BRAF基因突变率高于肿瘤直径<1 cm患者,差异具有统计学意义(P<0.05),而BRAF蛋白表达和基因突变、性别、淋巴结转移、血管内瘤栓和腺外浸润等无相关性。结论 BRAF基因突变仅发生在PTC中,其可能对PTC的诊断、治疗及预后判定提供新的理论依据。

Purpose To investigate the correlation between BRAF mutation and the biological behavior of the papillary thyroid carcino- ma（PTC）. Methods To collected 107 eases of the formalin-fixed paraffin-embedded tissues from the patients with thyroid disease, that included 93 cases of PTC, 5 eases of thyroid follicular cancer, 1 case of medullary carcinoma and 8 eases of thyroid adenoma, and detected the BRAF mutation in the tissues by immumohistochemistry, nested-primer PCR and gene sequencing. Results In 93 eases of PTC, BRAF protein expressed in 30 eases, with positive rate of 32. 3% , only in one ease of thyroid follicular carcinoma the expres- sion of BRAF protein was positive （20%）, and all negative in medullary carcinoma and thyroid adenoma. There were 30 （32. 3% , ） eases of BRAF mutation in 93 eases of PTC, and there were no BRAF mutation in the other type of the thyroid disease. The expression rate of BRAF protein and the BRAF mutation rate in the patients whose age was under 45 were significantly higher than whose age was over 45. And the expression rate of BRAF protein and the BRAF mutation rate of the patients whose tumor size was over 1 cm were sig- nificantly higher than whose tumor size was under 1 em, and the difference was statistically significant （ P 〈 0. 05 ）. There was no sig- nificant relationship between BRAF protein expression, gender, lymph node metastasis, intravascular tumor thrombus, and infiltration outside of the glands, and there was no significant relationship between BRAF mutation, gender, lymph node metastasis, intravaseular tumor thrombus, and infiltration outside of the glands. Conclusion BRAF mutation occurs only in PTC in this study, which may pro- vide a new theoretical basis for the diagnosis, treatment and prognosis of the PTC.