MASA-PCR检测甲状腺乳头状癌中BRAF^(V600E)点突变的研究

BRAF^(V600E) Mutation in Papillary Thyroid Cancer by MASA-PCR

采用突变等位基因特异性扩增法(mutant allele specific amplication,MASA-PCR)检测了125例甲状腺石蜡包埋组织中BRAFV600E点突变(包括94例甲状腺癌,15例甲状腺腺瘤,15例结节性甲状腺肿和1例癌旁正常组织),探讨甲状腺乳头状癌(PTC)与其临床病理学特征之间的关系。结果发现,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68.4%(57/83),主要见于经典型PTC和微小癌,其突变率分别为73%(52/71)和2/3,在其它类型的甲状腺癌及良性病变中均未检测到BRAFV600E突变。临床病理资料显示,患者发病平均年龄为45岁,突变率在40岁以上者显著高于40以下者(χ2=4.69,P<0.05),而与性别、淋巴结转移、慢性淋巴细胞浸润无显著关系(P<0.05)。结果显示,1)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,可为PTC的发生机制提供新的视点。2)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。

Abstract： To detect the frequency of BRAF^V600E mutation in papillary thyroid cancer and other kinds of benign and malignant thyroid disease and to explore their correlation with the clinicopathologic features of papillary thyroid cancer （PTC）, MASA-PCR was used in formalin-fixed, paraffin-embedded biopsy samples in 125 cases thyroid disease, which included 94 cases of thyroid caicinoma, 15 cases of follicular adenomas, 15 cases of benign nodular goiters and 1 case of normal tissue beside caicinoma. The results showed BRAF^V600E mutation was detected only in PTC（68.4 %, 57/83）and 1 case of an aplastic thyroid cancer had a high prevalence in both classic and microcarcinoma（2/3）. However,other kinds of thyroid cancer and benign thyroid diseases were negative for BRAF^V600E mutation. According to the clinicopathologic data, the mean age of patients with BRAF^V600E mutation （ ≥40 years old） was significantly higher than those who didn＇t present mutation（ 〈 40 years old）, Meanwhile, statistic data didn＇t show any con＇elation between the BRAF^V600E mutation and clinicopathologic featuers such as gender, tumor size, node metastasis. The conclusion showed： （ 1 ） BRAF^V600E mutation only occurred in PTC and some anaplastic thyroid cancer. The high prevalence of BRAF^V600E mutation indicates it＇s an important and common molecular genetic hallmark of PTC, so it can be used in diagnosis and differential dia gnosis. （2） BRAF^V600E mutation frequency was high in classic and microcarcinoma of PTC, which inferred that the BRAF^V600E mutation maybe play an important role in their etiopathogenesis.