甲状腺乳头状癌的浸润性滤泡变异型（IFVPTC）表现出甲状腺乳头状癌（PTC）典型的核特征，但表现出滤泡生长模式。具有非典型PTC核特征的IFVPTC的诊断对术前细胞病理学和术后组织病理学都提出了挑战。在这种情况下，需要分子标记来辅助诊断。鉴于对 IFVPTC 基因组特征的了解有限，本研究旨在表征其遗传改变并鉴定临床相关分子标记。对 50 个 IFVPTC 肿瘤-正常对进行全外显子组测序，鉴定出单核苷酸变异、体细胞拷贝数改变 (sCNA) 和亚克隆结构。通过聚合酶链反应和桑格测序验证了关键突变，而通过免疫组织化学（IHC）验证了有价值的生物标志物。这项研究发现，在肿瘤发生过程中，内源过程而不是外源诱变剂主导了 IFVPTC 基因组的形成。 BRAF V600E是IFVPTC中唯一常见的主干突变和显着突变的基因。亚克隆分析发现，大多数 IFVPTC 样本含有两个或多个共存克隆。 sCNA 分析显示人类白细胞抗原 C (HLA-C) 和 HLA-A 显着扩增。随后的 IHC 研究表明，HLA-C 有望避免将难以解释的 IFVPTC 和侵袭性包膜滤泡变异型 PTC (I-EFVPTC) 错误分类为具有乳头状核特征的非侵袭性滤泡性甲状腺肿瘤 (NIFTP)。尽管经典 PTC 和 IFVPTC 之间存在一些相似之处，但它们在 sCNA 模式上存在显着差异。这项研究为 IFVPTC 的基因改变提供了宝贵的见解，并强调了 HLA-C IHC 区分难以解释的 IFVPTC 和 I-EFVPTC 的潜力。 NIFTP，这将增强对其分子特征的理解，以改进诊断和管理。© 2024 美国癌症协会。

Infiltrative follicular variant of papillary thyroid carcinoma (IFVPTC) exhibits nuclear characteristics typical of papillary thyroid carcinoma (PTC) but demonstrates a follicular growth pattern. The diagnosis of IFVPTC presenting with atypical nuclear features of PTC poses challenges for both preoperative cytopathology and postoperative histopathology. In such cases, molecular markers are needed to serve as diagnostic aids. Given the limited knowledge of IFVPTC's genomic features, this study aimed to characterize its genetic alterations and identify clinically relevant molecular markers.Whole-exome sequencing of 50 IFVPTC tumor-normal pairs identified single-nucleotide variants, somatic copy number alterations (sCNAs), and subclonal architecture. Key mutations were verified via polymerase chain reaction and Sanger sequencing, whereas valuable biomarkers were validated via immunohistochemistry (IHC).This study found that endogenous processes rather than exogenous mutagens dominated the shaping of the genome of IFVPTC during tumorigenesis. BRAF V600E was the only common trunk mutation and significantly mutated gene in IFVPTC. Subcloning analysis found that most IFVPTC samples harbored two or more coexisting clones. sCNA analysis revealed that human leukocyte antigen C (HLA-C) and HLA-A were significantly amplified. Subsequent IHC investigations indicated that HLA-C shows promise in averting the misclassification of challenging-to-interpret IFVPTC and invasive encapsulated follicular variant of PTC (I-EFVPTC) as noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP). Although there were several similarities between classic PTC and IFVPTC, they differed significantly in their sCNA patterns.This study provides valuable insights into IFVPTC's genetic alterations and highlights the potential of HLA-C IHC to distinguish challenging-to-interpret IFVPTC and I-EFVPTC from NIFTP, which will enhance the understanding of its molecular features for improved diagnosis and management.© 2024 American Cancer Society.