RAS point mutations and PAX8-PPARγ rearrangement in thyroid tumors:: Evidence for distinct molecular pathways in thyroid follicular carcinoma
RAS point mutations and PAX8-PPARγ rearrangement in thyroid tumors:: Evidence for distinct molecular pathways in thyroid follicular carcinoma
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DOI：
10.1210/jc.2002-021907
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发表时间：
2003-05-01
影响因子：
5.8
通讯作者：
Nikiforov, YE
中科院分区：
文献类型：
--
作者：
Nikiforova, MN;Lynch, RA;Nikiforov, YE
采用分子生物学方法分析了一系列88例常规滤泡和Hurthle细胞甲状腺肿瘤的RAS突变和PAX 8-PPARgamma重排，并通过免疫组化分析了半乳糖凝集素-3和HBME-1的表达。开发了一种新的基于LightCycler技术的方法来检测H-RAS、K-RAS和N-RAS基因的密码子12/13和61中的点突变。49%的传统滤泡癌有RAS突变，36%有PAX 8-PPARgamma重排，只有1例（3%）两者都有。在滤泡性腺瘤中，48%有RAS突变，4%有PAX 8-PPARgamma重排，48%两者都没有。具有PAX 8-PPARgamma的滤泡癌通常表现出半乳糖凝集素-3的免疫反应性，但不表现出HBME-1的免疫反应性，倾向于出现在较年轻的患者年龄和较小的尺寸，并且几乎总是明显的侵袭性。相比之下，RAS突变的滤泡性癌最常显示HBME-1阳性/半乳糖凝集素-3阴性免疫表型，并且是最小或明显侵入性的。Hurthle细胞肿瘤很少有PAX 8-PPARgamma重排或RAS突变。这些结果表明，传统的滤泡性甲状腺癌的发展，通过至少两个不同的和几乎不重叠的分子途径，无论是RAS点突变或PAX 8-PPARgamma重排启动。
A series of 88 conventional follicular and Hurthle cell thyroid tumors were analyzed for RAS mutations and PAX8-PPARgamma rearrangements using molecular methods and for galectin-3 and HBME-1 expression by immunohistochemistry. A novel LightCycler technology-based method was developed to detect point mutations in codons 12/13 and 61 of the H-RAS, K-RAS, and N-RAS genes. Forty-nine percent of conventional follicular carcinomas had RAS mutations, 36% had PAX8-PPARgamma rearrangement, and only one (3%) had both. In follicular adenomas, 48% had RAS mutations, 4% had PAX8-PPARgamma rearrangement, and 48% had neither. Follicular carcinomas with PAX8-PPARgamma typically showed immunoreactivity for galectin-3 but not for HBME-1, tended to present at a younger patient age and be smaller size, and were almost always overtly invasive. In contrast, follicular carcinomas with RAS mutations most often displayed an HBME-1-positive/galectin-3-negative immunophenotype and were either minimally or overtly invasive. Hurthle cell tumors infrequently had PAX8-PPARgamma rearrangement or RAS mutations. These results suggest that conventional follicular thyroid carcinomas develop through at least two distinct and virtually nonoverlapping molecular pathways initiated by either RAS point mutation or PAX8-PPARgamma rearrangement.