While minimally invasive follicular thyroid cancer (miFTC) generally has low risk of recurrence or death, encapsulated angioinvasive (eaFTC) or widely invasive (wiFTC) histological subtypes display significantly worse prognosis. Drivers of invasion are incompletely understood. Therefore, tissue samples including miFTC, eaFTC, and wiFTC tumors, as well as histologically normal thyroid adjacent to benign follicular adenomas, were selected from a cohort (n = 21) of thyroid tumor patients, and the gene expression of selected transcription factors was characterized with quantitative PCR. Invasion-relevant spatial expression patterns of selected transcription factors were subsequently characterized with immunohistochemistry. E2F1 was over-expressed in all 3 subtypes (p<0.01). SP1 was differentially expressed in eaFTC and wiFTC compared with normal (p=0.01 and 0.04, respectively). TCF7L2 was significantly upregulated in wiFTC specifically (p<0.05). While these findings were mRNA specific, immunohistochemistry of additional cancer-associated transcription factors revealed differential expression along the tumor invasive front relative to the central tumor, and histone acetylation modulators emerged as putative invasion markers. These findings may have significant implications for the interpretation of bulk gene expression analysis of thyroid tumor samples or for the development of targeted therapeutics for this rare but aggressive thyroid cancer variant.

虽然微创滤泡性甲状腺癌 (miFTC) 通常复发或死亡的风险较低，但包裹性血管浸润性 (eaFTC) 或广泛浸润性 (wiFTC) 组织学亚型的预后明显较差。入侵的驱动因素尚不完全清楚。因此，从 甲状腺肿瘤患者的队列（n = 21）中选择了包括miFTC、eaFTC和wiFTC肿瘤在内的组织样本，以及与良性滤泡腺瘤相邻的组织学正常的甲状腺，并对所选转录因子的基因表达进行了表征与定量 PCR。随后用免疫组织化学表征了选定转录因子的入侵相关空间表达模式。E2F1在所有 3 个亚型中过表达（p<0.01)。与正常相比，SP1在 eaFTC 和 wiFTC 中差异表达（分别为p = 0.01 和 0.04）。TCF7L2在 wiFTC 中显着上调（p <0.05）。虽然这些发现是 mRNA 特异性的，但其他癌症相关转录因子的免疫组织化学显示，相对于中央肿瘤，沿肿瘤侵袭前沿存在差异表达，并且组蛋白乙酰化调节剂作为假定的侵袭标志物出现。这些发现可能对解释甲状腺肿瘤样本的大量基因表达分析或开发针对这种罕见但具有侵袭性的甲状腺癌变体的靶向治疗方法具有重要意义。