甲状腺乳头状癌中BRAF~(V600E)点突变的研究

目的:探讨BRAFV600E点突变与甲状腺乳头状癌(PTC)及其临床病理学特征之间的关系。方法:采用突变等位基因特异性扩增法(MASA-PCR)检测108例甲状腺石蜡包埋组织中BRAFV600E点突变(包括83例甲状腺癌,11例甲状腺腺瘤,13例结节性甲状腺肿和1例癌旁正常组织)。结果:仅在PTC和1例甲状腺未分化癌中检测到BRAFV600E突变,PTC中突变率为66.7%(48/72),主要见于经典型PTC和微小癌,其突变率分别为72.6%(45/62)和66.7%(2/3),在其它类型的甲状腺良恶性病变中均未检测到BRAFV600E突变。40岁以上患者的BRAFV600E突变率显著高于40岁以下者,而与性别、淋巴结转移、慢性淋巴细胞浸润无显著关系。结论:BRAFV600E突变仅发生于PTC和部分未分化癌,是PTC中较常见的遗传学事件,为PTC的发生机制提供新思路。BRAFV600E突变主要见于经典型PTC和微小癌,可能是甲状腺乳头状癌表型的重要决定因素之一。

Study of BRAFV600E mutation in papillary thyroid cancer

Objective:To explore the frequency of BRAFV600E mutation in PTC and its correlation with the clinicopathologic features of PTC.Methods:MASA-PCR was performed in formalin-fixed,paraffin-embedded biopsy samples in 108 cases thyroid disease,which included 83 cases of thyroid caicinoma,11 cases of follicular adenomas,13 cases of benign nodular goiters and 1 case of normal tissue beside caicinoma.Results:BRAFV600E mutation was detected only in PTC(66.7%,48/72)and had a high prevalence in both classic of PTC and microcarcinoma.However,other kinds of thyroid cancer and benign thyroid diseases were negative for BRAFV600E mutation.The mean age of patients with BRAFV600E mutation(≥40 y)was significantly higher than that without mutation(< 40 y),Meanwhile,statistic data didn't show any correlation between the BRAFV600E mutation and clinicopathologic featuers such as gender,tumor size,node metastasis.Conclusion:BRAFV600E mutation only occurred in PTC and some anaplastic thyroid cancer.The high prevalence of BRAFV600E mutation indicates that it's an important and common molecular genetic hallmark of PTC,which will put up a new viewpoint to its genesis and can be used in diagnosis and differential diagnosis.BRAFV600E mutation frequency is high in classic PTC and microcarcinoma,which inferred that the BRAFV600E mutation maybe play an important role in their etiopathogenesis.