[1122] Epigenetic Regulation of Chromatin Structure in Tumorigenesis: Polycomb Group Protein EZH2 and Heterochromatin Protein 1 Expression in Malignant Thyroid Lesions

A Contreras, T Kroll, M Tretiakova. University of Chicago, Chicago, IL

Background: Epigenetic regulation of chromatin structure plays an important role in tumorigenesis and tumor progression. The polycomb group protein EZH2, which regulates chromatin structure by methylating histones H3 and H1, is upregulated in a variety of tumors, including breast, prostate, and bladder. In addition, heterochromatin protein1 (HP1), which induces heterochromatin formation by binding to histones and thereby downregulates transcription, is lost in various tumors. In order to further understand the role that chromatin structure plays in thyroid cancer, we analyzed the expression of EZH2 and HP1 in thyroid cancer progression.
Design: Thyroid tissue microarrays (TMA) were built to include follicular adenomas (FA, N=19), Hurthle cell adenomas (HA, N=11), follicular carcinomas (FC, N=22), Hurthle cell carcinomas (HC, N=9), papillary carcinomas (PC, N=31), poorly differentiated and anaplastic tumors (PD/AN, N=10), colloid nodules (CN, N=5) and normal adjacent thyroid tissue (NT, N=80). Immunostaining was performed with antibodies for EZH2 (rabbit monoclonal, ZMD.309) and HP1 (rat monoclonal, MAC 353). Nuclear expression of EZH2 was scored as % positive nuclei using Automated Cellular Imaging System (ACIS, Clarient). Intensity of anti-HP1 staining was graded as 0, 1+, 2+ or 3+.
Results: In all thyroid lesions examined, there was a statistically significant increase in EZH2 expression when compared to NT (p<0.01). Furthermore, except in the case of FA, levels of HP1 beta were significantly decreased in all thyroid lesions when compared to NT (p<0.01). See graph below for the combined data.


Conclusions: Thyroid carcinomas exhibit significantly increased EZH2 expression, consistent with observations in other tumor types. EZH2 has been proposed to have a nonproliferative function in tumor progression. Interestingly, non-carcinomatous thyroid lesions also have increased EZH2. Thus, while EZH2 may not be sufficient for tumor initiation, increased EZH2 may play a role in tumor promotion, most likely by controlling gene expression. Similarly, the loss of HP1 in thyroid carcinomas is hypothesized to result in altered gene expression that promotes tumorigenesis.
Category: Head & Neck

Monday, March 9, 2009 1:00 PM

Poster Session II # 179, Monday Afternoon