Molecular genotyping of papillary thyroid carcinoma follicular variant according to its histological subtypes (encapsulated vs infiltrative) reveals distinct BRAF and RAS mutation patterns.
Molecular genotyping of papillary thyroid carcinoma follicular variant according to its histological subtypes (encapsulated vs infiltrative) reveals distinct BRAF and RAS mutation patterns.
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DOI：
10.1038/modpathol.2010.112
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发表时间：
2010-09
期刊：
影响因子：
--
通讯作者：
Ghossein RA
中科院分区：
文献类型：
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作者：
Rivera M;Ricarte-Filho J;Knauf J;Shaha A;Tuttle M;Fagin JA;Ghossein RA
滤泡型乳头状甲状腺癌通常表现为包膜肿瘤，较少表现为部分/非包膜浸润性肿瘤。被包膜的肿瘤很少转移到淋巴结，而浸润性肿瘤通常有淋巴结转移。滤泡性变异体的分子图谱与滤泡性腺瘤/癌组相似，具有高RAS和极低的BRAF突变率。根据其包膜和浸润性形式，还没有对滤泡型乳头状甲状腺癌的致癌突变进行全面的调查。对28例包膜型和19例浸润性滤泡变异型的石蜡组织进行了RET、BRAF、NRAS、HRAS、KRAS、PIK3CA、AKT1等11个癌基因突变的质谱仪基因分型。包膜或浸润性肿瘤在年龄、性别、肿瘤大小和血管侵犯方面无差异。浸润性癌甲状腺外侵犯、切缘阳性和结节转移的发生率明显高于包膜型肿瘤(P<；0.05)。BRAF 1799T>；A突变在19例浸润性肿瘤中有5例(26%)，在包膜癌中无一例发生突变(P=0.007)。Ras基因突变在包膜组中为36%(10/28)，在浸润性肿瘤中为10/19(P=0.09)。1例包膜性癌显示PAX8/PPARγ重排，2例浸润性癌融合。被包裹的滤泡型乳头状甲状腺癌具有与滤泡性腺瘤/癌非常接近的分子特征(RAS发生率高，没有BRAF突变)。浸润性滤泡变异型与滤泡性腺瘤/癌(BRAF>；RAS突变)更接近经典乳头状甲状腺癌，具有相反的分子特征。包膜型和浸润型滤泡的分子图谱与其生物学行为(即转移结节和侵袭型)相似。
The follicular variant of papillary thyroid carcinoma usually presents as an encapsulated tumor and less commonly as a partially/non-encapsulated infiltrative neoplasm. The encapsulated form rarely metastasizes to lymph node, whereas infiltrative tumor often harbors nodal metastases. The molecular profile of the follicular variant was shown to be close to the follicular adenoma/carcinoma group of tumors with a high RAS and very low BRAF mutation rates. A comprehensive survey of oncogenic mutations in the follicular variant of papillary thyroid carcinoma according to its encapsulated and infiltrative forms has not been performed. Paraffin tissue from 28 patients with encapsulated and 19 with infiltrative follicular variant were subjected to mass spectrometry genotyping encompassing the most significant oncogenes in thyroid carcinomas: 111 mutations in RET, BRAF, NRAS, HRAS, KRAS, PIK3CA, AKT1 and other related genes. There was no difference in age, gender, tumor size and angioinvasion between encapsulated or infiltrative tumors. Infiltrative carcinomas had a much higher frequency of extrathyroid extension, positive margins and nodal metastases than encapsulated tumors (P<0.05). The BRAF 1799T>A mutation was found in 5 of 19 (26%) of the infiltrative tumor and in none of the encapsulated carcinomas (P=0.007). In contrast, RAS mutations were observed in 10 of 28 (36%) of the encapsulated group (5 NRAS_Q61R, 3 HRAS_Q61, 1 HRAS_G13C and 1 KRAS_Q61R) and in only 2 of 19 (10%) of infiltrative tumors (P=0.09). One encapsulated carcinoma showed a PAX8/PPARγ rearrangement, whereas two infiltrative tumors harbored RET/PTC fusions. Encapsulated follicular variant of papillary thyroid carcinomas have a molecular profile very close to follicular adenomas/carcinomas (high rate of RAS and absence of BRAF mutations). Infiltrative follicular variant has an opposite molecular profile closer to classical papillary thyroid carcinoma than to follicular adenoma/carcinoma (BRAF>RAS mutations). The molecular profile of encapsulated and infiltrative follicular variant parallels their biological behavior (ie, metastatic nodal and invasive patterns).