PAX8-PPARγ rearrangement in thyroid tumors -: RT-PCR and immunohistochemical analyses

PAX8-PPARγ rearrangement in thyroid tumors -: RT-PCR and immunohistochemical analyses
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DOI:
10.1097/00000478-200208000-00006
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发表时间:
2002-08-01
影响因子:
5.6
通讯作者:
Nikiforov, YE
Nikiforov, YE
中科院分区:
医学1区
文献类型:
--
作者:
Nikiforova, MN;Biddinger, PW;Nikiforov, YE

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最近在滤泡性甲状腺癌中发现了PAX 8-PPARgamma重排,但在滤泡性腺瘤或其他甲状腺肿瘤中未发现。我们在这里报告的分析PAX 8-PPARgamma在一系列的118甲状腺肿瘤使用新开发的RT-PCR检测这种重排在冷冻和石蜡包埋组织和使用免疫染色与PPARgamma抗体。通过RT-PCR在15例滤泡癌中的8例(53%)和25例滤泡腺瘤中的2例(8%)中检测到PAX 8-PPARgamma,但在35例乳头状癌(包括12例滤泡变体)、12例Hurthle细胞癌、12例Hurthle细胞腺瘤、2例间变性癌、1例低分化癌或16例增生结节中未检测到PAX 8-PPARgamma。有辐射暴露史的滤泡癌患者的患病率较高(三分之三)。用PPARgamma抗体进行的强的、弥散的核免疫染色与通过RTPCR检测到的PAX 8-PPARgamma的存在相关。大多数PAX 8-PPARgamma阳性的散发性滤泡癌是明显侵袭性的,而缺乏重排的肿瘤主要是微创的。PAX 8-PPARgamma阳性的两个滤泡性腺瘤具有小梁状生长模式和厚包膜,但没有侵袭,因此可能代表“浸润前”滤泡性癌。在Hurthle细胞瘤和乳头状甲状腺癌中PAX 8-PPARgamma重排的缺乏突出了这些甲状腺肿瘤的分子发病机制的差异。
A PAX8-PPARgamma rearrangement has been recently identified in follicular thyroid carcinomas, but not in follicular adenomas or other thyroid tumors. We report here the analyses of PAX8-PPARgamma in a series of 118 thyroid tumors using a newly developed RT-PCR assay to detect this rearrangement in frozen and paraffin-embedded tissues and using immunostaining with a PPARgamma antibody. PAX8-PPARgamma was detected by RT-PCR in eight of 15 (53%) follicular carcinomas and two of 25 (8%) follicular adenomas but not in 35 papillary carcinomas (including 12 follicular variants), 12 Hurthle cell carcinomas, 12 Hurthle cell adenomas, two anaplastic carcinomas, one poorly differentiated carcinoma, or 16 hyperplastic nodules. The prevalence was higher in follicular carcinomas from patients with a history of radiation exposure (three of three). Strong, diffuse nuclear immunostaining with the PPARgamma antibody correlated with the presence of PAX8-PPARgamma detected by RTPCR. Most sporadic follicular carcinomas positive for PAX8-PPARgamma were overtly invasive, whereas tumors lacking the rearrangement were predominantly minimally invasive. The two follicular adenomas positive for PAX8-PPARgamma had trabecular growth pattern and thick capsule, but no invasion, and thus may represent "pre-invasive" follicular carcinomas. The absence of PAX8-PPARgamma rearrangements in Hurthle cell tumors and papillary thyroid carcinomas highlights the differences in the molecular pathogenesis of these thyroid tumors.