1 Department of Surgical, Medical, Molecular Pathology and Critical Area, University of Pisa , Pisa, Italy .
2 Department of Laboratory Medicine, Anatomic Pathology, Azienda Ospedaliero Universitaria Pisana , Pisa, Italy .
Thyroid. 2017 Oct;27(10):1267-1276. doi: 10.1089/thy.2016.0605. Epub 2017 Sep 5.
The follicular variant (FV) of papillary thyroid cancer (PTC) is one of the most common variants of PTC. Clinically, non-infiltrative FVPTC is considered a low-risk variant of PTC, and the non-invasive encapsulated forms of FVPTC represent a group of thyroid tumors with a particularly good prognosis. Consequently, these neoplasms have been very recently reclassified as non-invasive follicular neoplasms with papillary-like nuclear features (NIFTP). From a molecular standpoint, NIFTP appears to be similar to follicular neoplasms. However, only limited data are currently available regarding their gene expression profile.
The aim of this study was to identify specific molecular signatures of 26 NIFTPs compared to those of 19 follicular adenomas (FAs) and 18 infiltrative FVPTCs (IFVPTCs). A nanoString custom assay was used to perform mRNA expression analysis. All cases were also genotyped for BRAF, N-, H-, and K-RAS mutations. Samples were grouped on the basis of gene expression profiles by Pearson's correlation and non-negative matrix factorization clustering analysis. Finally, the uncorrelated shrunken centroid machine-learning algorithm was used to classify the samples.
The results revealed distinct expression profiles of FAs and IFVPTCs. NIFTP samples can exhibit different expression profiles, more similar to FAs (FA-like) or to IFVPTCs (IFVPTC-like), and these different expression profiles largely depend on the presence of different mutations (RAS or BRAF).
In conclusion, although further validation of the model is required by using a larger group of prospective cases, these data reinforce the hypothesis that IFVPTC-like NIFTPs might represent precursors of IFVPTC.
滤泡型甲状腺癌（PTC）的滤泡变异型（FV）是 PTC 最常见的变异型之一。临床上，非浸润性 FVPTC 被认为是 PTC 的低风险变异型，而 FVPTC 的非侵袭性包膜形式代表了一组预后特别好的甲状腺肿瘤。因此，这些肿瘤最近被重新分类为具有乳头状核特征的非浸润性滤泡性肿瘤（NIFTP）。从分子角度来看，NIFTP 似乎与滤泡性肿瘤相似。然而，目前关于其基因表达谱的资料有限。
本研究的目的是鉴定 26 例 NIFTP 与 19 例滤泡性腺瘤（FA）和 18 例浸润性 FVPTC（IFVPTC）相比的特定分子特征。使用 nanoString 定制检测进行 mRNA 表达分析。所有病例还进行了 BRAF、N-、H-和 K-RAS 突变的基因分型。根据基因表达谱通过 Pearson 相关和非负矩阵分解聚类分析对样本进行分组。最后，使用不相关的收缩质心机器学习算法对样本进行分类。
结果显示 FA 和 IFVPTC 的表达谱明显不同。NIFTP 样本可以表现出不同的表达谱，更类似于 FA（FA 样）或 IFVPTC（IFVPTC 样），并且这些不同的表达谱在很大程度上取决于不同突变（RAS 或 BRAF）的存在。
总之，尽管需要使用更大的前瞻性病例组来进一步验证该模型，但这些数据强化了这样一种假设，即 IFVPTC 样 NIFTP 可能代表 IFVPTC 的前体。
