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首页> 外文期刊>Modern Pathology >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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Molecular genotyping of papillary thyroid carcinoma follicular variant according to its histological subtypes (encapsulated vs infiltrative) reveals distinct BRAF and RAS mutation patterns

机译：乳头状甲状腺癌滤泡变体的分子基因分型根据其组织学亚型（包囊型与浸润型）揭示了不同的BRAF和RAS突变模式

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The follicular variant of papillary thyroid carcinoma usually presents as an encapsulated tumor and less commonly as a partiallyon-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 (PBRAF 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).
机译：甲状腺乳头状癌的滤泡变体通常表现为包囊性肿瘤，较少见为部分/未包囊的浸润性肿瘤。包封的形式很少转移到淋巴结，而浸润性肿瘤通常具有淋巴结转移。滤泡变体的分子谱显示接近具有高RAS和非常低BRAF突变率的肿瘤的滤泡腺瘤/癌组。尚未根据甲状腺乳头状癌的囊化和浸润形式对卵泡变异中的致癌突变进行全面调查。对28例囊性囊化患者和19例浸润性卵泡变体患者的石蜡组织进行了基因分型，该基因分型涉及甲状腺癌中最重要的癌基因：RET，BRAF，NRAS，HRAS，KRAS，PIK3CA，AKT1和其他相关基因的111个突变。包囊或浸润性肿瘤之间的年龄，性别，肿瘤大小和血管浸润均无差异。浸润性癌的甲状腺外延伸，阳性切缘和淋巴结转移的频率要比包囊性肿瘤高（PBRAF 1799T>在19个浸润性肿瘤中有5个（26％）发现突变，而没有一个包囊性癌（P = 0.007）。相反，包囊组的28个中有10个（36％）（5个NRAS_Q61R，3个HRAS_Q61、1个HRAS_G13C和1个KRAS_Q61R）和10个中的2个（10％）观察到RAS突变。 （P = 0.09）。一种囊状癌表现出PAX8 /PPARγ重排，而两种浸润性肿瘤则具有RET / PTC融合。囊状甲状腺乳头状癌的囊状变体分子结构非常接近滤泡性腺瘤/癌（RAS和RAS发生率高）浸润性滤泡变体与典型的乳头状甲状腺癌相比，与滤泡性腺瘤/癌相比具有相反的分子谱（BRAF> RAS突变）。卵泡变异性与它们的生物学行为（即转移性淋巴结和浸润型）相似。

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