甲状腺乳头状癌BRAF基因突变及表达的临床意义研究

目的探讨BRAF基因点突变及B-raf蛋白表达在甲状腺乳头状癌发生中的临床意义。方法应用聚合酶链式反应(PCR)技术检测65例甲状腺病变石蜡组织中BRAF点突变,应用免疫组化方法检测112例甲状腺病变组织中B-raf蛋白的表达情况,并比较BRAF基因突变和B-raf蛋白表达的相关性。结果在46例甲状腺乳头状癌中有21例发生BRAF的点突变,突变率为45.7。BRAF基因突变位于第15外显子的1799位点,胸腺嘧啶突变为腺嘌呤(T1799A)。在结节性甲状腺肿和滤泡状癌中未检测到BRAF的突变。乳头状癌BRAF基因突变率与结节性甲状腺肿比较,差异具有统计学意义(P<0.05)。但是与患者的性别、年龄、组织学类型、淋巴结转移和肿瘤分期无相关性(P>0.05)。在乳头状癌、滤泡状癌和结节性甲状腺肿中B-raf蛋白表达阳性率分别为65.1、47.6和15.4。结果显示,乳头状癌B-raf蛋白阳性表达率与良性病变比较,差异具有统计学意义(P<0.05)。在乳头状癌中BRAF基因突变与B-raf蛋白表达水平呈正相关(P<0.05)。乳头状癌与滤泡状癌比较,B-raf蛋白表达水平两组间无统计学意义(P>0.05)。结论甲状腺乳头状癌BRAF基因突变率和蛋白表达水平的增高,提示BRAF基因在乳头状癌发病中可能发挥重要的作用。对甲状腺肿瘤的病理诊断也具有辅助价值。

Clinical significance of BRAF mutation and expression in papillary thyroid carcinoma

Objective To investigate the clinical significance of BRAF mutation and B-raf protein expression in tumorigenesis of papillary thyroid carcinoma(PTC).Methods PCR method was performed to detect BRAF mutation in 65 specimens of paraffin-embedded thyroid lesions.B-raf protein expression was immunohistochemically examined in 112 paraffin-embedded thyroid lesions.Results BRAF mutation was detected in 21 out of 46 PTC cases with a detection rate of 45.7%.It was negative in 6 cases of follicular carcinoma and 13 cases of nodular goiter.The mutation pattern was point mutation with the substitution of adenosine for thymidine base(T1799A).The difference between PTC and nodular goiter in BRAF mutation rate was statistically significance(P<0.05).BRAF mutation in PTC was not correlated with age,gender,histological type,regional lymph node metastasis and TNM staging,but it was related to B-raf protein expression.The positive rates of B-raf expression in PTC,follicular carcinoma and nodular goiter were 65.1%,47.6% and 15.4%,respectively.The difference between PTC and nodular goiter in B-raf protein expression was statistically significance(P<0.05).Conclusions BRAF mutation and enhanced B-raf protein expression in PTC suggest that BRAF gene might play an important role in the tumorigenesis of PTC.The detection of BRAF mutation and B-raf expression in thyroid tumors might be helpful for pathological diagnosis.