Overexpression of Histone H3 Lysine 27 Trimethylation Is Associated with Aggressiveness and Dedifferentiation of Thyroid Cancer

Abstract

A variety of epigenetic dysregulations are observed in thyroid malignancies. EZH2, the catalytic subunit of polycomb repressive complex 2, is upregulated in advanced thyroid cancers. EZH2 can catalyze trimethylation of histone H3 at lysine 27 (H3K27me3) and contribute to transcriptional silencing of target genes. Here, we investigated the immunohistochemical expression of H3K27me3 in neoplastic and normal thyroid tissues. Normal thyroid epithelial cells typically exhibited nuclear staining of moderate intensity. A similar expression pattern was observed in nodular goiters and follicular adenomas. By contrast, strong H3K27me3 expression was evident in 80% (8/10) lymphocytic thyroiditis, 63% (80/127) papillary thyroid cancer, 41% (7/17) follicular thyroid cancer, and 73% (8/11) poorly differentiated and anaplastic thyroid cancer. In differentiated thyroid cancer, strong H3K27me3 expression was associated with extrathyroidal extension (p\u2009<\u20090.001), lymphovascular invasion (p\u2009=\u20090.029), lymph node metastasis (p\u2009=\u20090.006), and higher risk of recurrence (p\u2009=\u20090.003). Our results indicate that H3K27me3 overexpression may be implicated in aggressiveness and dedifferentiation of thyroid cancer. In addition to prognostication, the predictive value of H3K27me3 expression deserves further investigation given the recent development of epigenetic targeting agents.